Researchers Report Alternate Explanation Discovery Of How And Why CCSVI Treatment Works In MS Patients

Researchers Report Alternate Explanation Discovery Of How And Why CCSVI Treatment Works In MS Patients

A new study may offer new insight on beneficial effects of “chronic cerebrospinal venous insufficiency” (CCSVI or CCVI) treatment for Multiple Sclerosis (MS) and certain other disease conditions. CCSVI is the controversial theory that blocked neck veins are a major factor in many MS cases proposed by Italian physician and researcher Dr. Paolo Zamboni in 2008 (and that according to report in the Lancet dates back to a hypothesis originally posed by Putnam in 1947) — the culmination of a ten year research quest toward finding a cure for MS that began when his wife was diagnosed in 1999. Dr. Zamboni’s initial study revealed venous abnormalities in almost 100% of the 65 patients with MS who participated, while no venous abnormalities were found in a control group. Dr. Zamboni postulated that a vein-widening procedure, venous angioplasty, which he called “liberation treatment,” could improve symptoms of MS patients.

The CCSVI procedure was originally thought to work via expanding a narrowed jugular vein, thus restoring proper flow of blood in the veins draining the central nervous system, but researchers have been unable reproduce these results in subsequent studies, calling the entire CCSVI as a cause of MS theory into question, and to date, there is still no conclusive evidence that CCSVI is a cause of MS, or even that it is a symptomatic condition in its own right.

ccsvitvamHowever, while the debate over CCSVI and MS continues, new data suggests that Dr. Zamboni may have gotten it right in looking at the veins for treatment, but it might not be venous abnormalities that are the real problem, with a team of California-based researchers contending that it is the nerves surrounding the veins not the veins themselves that are being treated by ballooning, with expansion of the jugular vein leading to stimulation of the autonomic nerve fibers, which run alongside the jugular and are responsible for communication between the brain and the central nervous system. They say that ongoing research and a growing body of clinical data strongly indicate that Dr. Zamboni’s CCSVI procedure may be the first viable treatment for an even more pervasive problem — dysautonomia — which is seen not only in almost all MS patients but also in patients diagnosed with a long list of other diseases and conditions. As a result, they believe the CCSVI procedure is better described by the term TVAM (Transvascular Autonomic Modulation).

journalofendovasculartherapyjune2014The new study, published in the June, 2014 edition of the Journal of Endovascular sheds light on the positive effect of CCSVI on the sympathetic nervous system, explaining how researchers were able to pinpoint how the procedure improved abnormal sympathetic function found in patients with many chronic conditions including Multiple Sclerosis.

Titled “Transvascular Autonomic Modulation: A Modified Balloon Angioplasty Technique for the Treatment of Autonomic Dysfunction in Multiple Sclerosis Patients” (Journal of Endovascular Therapy: June 2014, Vol. 21, No. 3, pp. 417-428), the study coauthored by Newport Beach, California based Interventional Radiologist, Michael Arata, MD, and his research associate, Zohara Sternberg, PhD, compares the efficacy of the TVAM procedure vs. traditional balloon angioplasty in improving cardiovascular autonomic nervous system (ANS) dysfunction in Multiple Sclerosis (MS) patients. Drs. Arata and Sternberg report that they found using an angioplasty balloon to stimulate vein-associated nerves increased sympathetic activity shows promise for patients who suffer from MS.

They note that twenty-one MS patients (11 men; mean age 48.713.0 years) who presented with symptoms of cardiovascular ANS dysfunction underwent TVAM and were compared with age/sex-matched MS patients (10 men; 49.311.1 years) in the same stages of the disease who presented with chronic cerebrospinal venous insufficiency (CCSVI) and who underwent venous balloon angioplasty.

The coauthors observe that in this instance, TVAM involved the coupling of balloon angioplasty of the internal jugular veins with application of external manual compression and dilation of the azygos and renal veins; unlike traditional angioplasty for CCSVI, which treats only abnormal veins (50% stenosis or static valve), all targeted vessels were treated with TVAM regardless of the presence of an abnormality. The effect of TVAM on ANS function was indicated by determining heart rate variability based on the electrocardiographic R-R interval lengths using vector analysis to derive the mean circular resultant (MCR) and the expiration/inspiration (E/I) ratio, the Valsalva ratio, and the 30:15 postural ratio at 24 hours after intervention.

They found that left renal vein compression was common among the TVAM patients and resulted in 50% luminal compromise in 10 of 21 patients. A, and overall, 18 patients met the diagnostic criteria for CCSVI with at least one lesion >50%, but only 10 lesions were considered treatable by traditional balloon angioplasty. After intervention, they report that R-R interval values, including the 30:15 postural ratio (p=0.01), the MCR (p=0.1), and E/I ratio (p=0.1), were higher for the TVAM patients compared to the control group, and the safety profile of the TVAM procedure was similar to that of traditional balloon angioplasty.

Drs. Arata and Sternberg conclude that the combination of balloon angioplasty of anatomically normal veins coupled with external compression during dilation of these veins can improve indicators of ANS dysfunction, reporting that the safety and efficacy of TVAM in MS patients observed in this pilot study is encouraging, paving the way for the treatment of dysautonomia in pathological states other than MS.

[adrotate group=”4″]

They suggest that further studies should investigate TVAM in a larger MS cohort, and that the improved R-R intervals post-TVAM achieved in this study, combined the results of their recent study showing arterial blood pressure increase post venous angioplasty in MS patients with below-normal baseline pressure readings, strengthen the notion that angioplasty exerts beneficial effects by improving ANS function, and that the safety of this modified procedure, coupled with its efficacy observed in this pilot study, suggests its utility in improving symptoms of ANS dysfunction, noting that this modified technique could be further applied in other autoimmune and neurological diseases where dysautonomia plays a role in disease pathophysiology.

However, they caution that the long-term effects of cerebral venous distension are currently unknown, and one cannot exclude the possibility that the increase in vagal activity post angioplasty may further disturb the autonomic balance in selected MS patients who initially present with reduced sympathetic ANS function, and additional study and replication of these results are required.

DrArataA graduate of UCSF School of Medicine, Dr. Arata has spent more than a decade performing angioplasty and has been at the forefront of research for CCSVI. “There is a possibility that improved autonomic function may diminish symptoms and have an impact on the course of the disease,” comments Dr. Arata, who serves as Medical Director at Synergy Health Concepts in Newport Beach. He is the most experienced CCSVI physician in the United States having performed more than 2000 procedures on patients with autonomic-associated disease, claiming a high clinical (patient response) success rate in excess of 90% in a recent study group.

“The current study demonstrates the procedure’s effect on autonomic function, offering an explanation for why patients may see symptom improvement with venous ballooning even though separate studies have failed to show a relationship between venous obstruction and Multiple Sclerosis. The mechanism of symptom improvement is improved autonomic tone rather than relief of flow obstruction,” says Dr. Arata.

SynergyHealth

Synergy Health Concepts, located in Newport Beach, CA, is a state-of-the-art medical center for CCSVI diagnosis and treatment, fully equipped with four patient examination rooms, three procedure rooms, and seven pre-procedural and post-procedural recovery suites. SHC’s state-of-the-art 3 Tesla MRI and ultrasound machines enable the clinicians to obtain the best imaging possible for patients, and SNC claims to be the only practice using autonomic testing as a core component of the diagnostic evaluation.

SHC reports maintaining a a 99 percent technical success rate in more than 2000 procedures performed, and a clinical (patient response) success rate in excess of 90%, and that in patients showing autonomic symptoms who test positive for autonomic dysfunction who are approved for the procedure, symptom relief begins during and directly after the procedure, and is durable in excess of 2 years for more than 75% of patients.

The CCSVI procedure (TVAM) is performed on an outpatient basis at Synergy Health’s state-of-the-art medical center. The patient will receive conscious sedation to maintain comfort throughout the procedure, and the procedure will typically take under an hour to perform. The primary treatment is an endovascular procedure in which a catheter is inserted via a small incision and threaded up into the jugular vein. A balloon is then inflated via the catheter, expanding the jugular vein in much the same way that coronary angioplasty expands narrowed arteries of the heart.

SVI says the majority of their patients (about 75 percent) have a durable response, some lasting over three years and beyond with no degradation or relapse, and this cohort is able to maintain benefits of the procedure seen from day one. However, the remaining 25 percent of patients don’t respond to treatment as well, with about 10 percent experiencing no benefits at all post procedure.

For more information, visit:
http://www.synergyhealthconcepts.com/

Sources:
Synergy Health Concepts
Journal of Endovascular Therapy
Wikipedia
Lancet

Image Credits:
Synergy Health Concepts

43 comments

  1. Stephen Lovatt says:

    My personal opinion of this TVAM is it is Nonsense! A made up condition to to keep gullible patients coming through the door now that the amount of patients seeking the CCSVI ‘liberation therapy’ as steadily waned off. I doubt that no other independent researchers would ever seriously consider his theory long enough to launch an investigation that would confirm or deny his data.

      • Stephen Lovat says:

        Lynne, Your comments become more outlandish the more your post. Lawsuits against naysayers for a subjective procedure that cannot demonstrate long term benefit in more than about 10% of patients after 18 months post treatment. For your information I have received the CCSVI procedure on 3 occasions once at Synergy. With out a viable way to prevent re-sternosis most patients will be lucky to experience benefits past 90 days. Some clinics performing this procedure may as well establish a second follow up procedure before the patient leaves the first time.
        Finally, Arata has neither attended nor presented his research to the International Society for Neurovascular Disease (ISNVD) at recent annual conferences despite many presentations on the subject of CCSVI by respected clinicians such as Robert Zivadinov, Paolo Zamboni, Marian Simka, Adnan Siddiqui, Mark Haacke, Aldo Bruno, Tomasz Ludyga, and Clive Beggs among others. These physicians are his colleagues who are genuinely interested in the CCSVI association with MS…but no Michael Arata despite his new and novel vascular therapy that he promotes as significant in its effect on MS as well as a host of other neurodegenerative diseases.

    • LYNNE HEAL says:

      Stephen your remarks to me are classed as disabled hatred and an offence which is also someone showing no compassion towards someone like myself whos diasabled. I nearly lost my life in 2010 with MS. I personally find your remarks very disturbing indeed

    • Denise Baillie says:

      Really!? So the fact that I was immediately able to discard not only my walker, but also my canes immediately following my TVAM treatment more than 2 years ago is all in my imagination? Rebooting my Autonomic system with this treatment was literally like someone flicking a switch from ‘sick’ to ‘healthy’ and I haven’t looked back since! After 4 years on CPP Disability I was able to return to work full time, get myself a new bicycle and return to the mountains to go hiking! You neglect to let anyone know when you got your TVAM treatment; just that you had CCSVI treatment 3 times, which is know to decrease in effectiveness with each subsequent treatment! Keep your sour grapes to yourself!

      • Shannon says:

        You received tvam? Asking because I am very interested in it for MS. I’m attempting to raise the money now. Were you treated for MS?

  2. Brian White says:

    It worked really well for my wife. Doctor said her veins were fine but they treated her because she met the autonomic dysfunction criteria. She could barely walk a block at the time and had the “MS walk” rotten balance and drop-foot, and often fell on short walks. Nearest thing to a miracle that I ever experienced. Her cold dead right side got warm again too.

  3. Lori Batchelor says:

    I believe the TVAM procedure helps both blood flow and stimulation of the vagus nerve. If proper blood flow continues, then the nerve continues to be stimulated. The only thing that has ever helped any of my MS symptoms, in any long-term way, since I was diagnosed in 1990, becoming secondary/progressive (and, therefore, not qualified for any disease-modifying drug therapy) in the mid-90′s, was venous angioplasty for CCSVI in March, 2011. Overnight, my balance returned. My heat intolerance was eliminated. Drop-foot improved dramatically. My emotions stabilized, allowing me to kick my 16-year Prozac habit–allowing me to be completely drug-free and I haven’t had one of my “MS headaches”, that I used to get almost weekly, since treatment. I am very active with swimming and Aquafit now, to keep my blood flowing. My EDSS (disability) score went from 6.5 to 4, which is supposedly not possible for someone with s/p MS but I proved them wrong!

    • Dagmar Lofts says:

      That is great Lori. Thanks for telling your story. I believe the doctors have more work to do in the CCSVI area and that all our MS stories are similar, yet different, leads me to believe not everything is discovered in their technique. I keep my prayers going so that the Lord will help the doctors that want to help us.

  4. Brian White says:

    My wife had treatment from Dr Arata. She has an MS like illness. We had the treatment in August 2013 and the results were miraculous. She regained feeling in her feet and balance the next day. She could empty her bladder again and how her entire right side felt to me was entirely different. For the first time in 4 years her right arm was warm! Dr Arata has treated over 2000 people. (By the way, my wife was convinced that she had stenosis and he told her that actually her veins were fine). Her blood flow issues were caused by the vagus nerve mis-communation to the brain). Remember that those blood flow issues are everywhere, legs, feet, hands, and inside the brain itself. Her heat intolerance and brain fog was magically disappeared away too! Dr Arata is quite happy to train other doctors how to do this. (learning curve in his case was about 200 procedures to be really competent, so a logical medical system would send people to him to get trained. ) I have videos of my wife before and after, and also a playlist of other people who had it done. The most significant one for me is Dawn Skinner, who has had no symptoms in about 3 years following her procedure in New York. She is now a friend of mine on facebook and I asked her recently how she is doing. So currently it is a roulette game, 90% of people going to Arata show clinical improvement (get at least somewhat better), but he pre-screens people. If you have MS and no pre-screening your chances are 1/3 no improvement , 1/3 some improvement and 1/3 great improvement. There is also a chance that the effects will not last. It became clear to me on research that my wife had mostly autonomic symptoms and I was confident going in that it was money well spent. BUT, I was not expecting the miracle that we got!

  5. Stephen Lovatt says:

    Here’s what Dr Broeska thinks about the treatment.
    Arata’s hypothesis proposes that MS is primarily an autonomic nervous system (ANS) disorder and does not recognize the current prevailing abundance of research indicating that blood-brain barrier disruption, microglial activation and immune responses leading to inflammation, demyelination and neurodegeneration are fundamental to symptomatic development of MS. In his research, Arata proposes that ballooning the jugular veins prompts stimulation of autonomic nerve fibers that run parallel to cervical veins and have a direct role in communication between the brain and the rest of the central nervous system. His published conclusions indicate that “the combination of balloon angioplasty of anatomically normal veins coupled with external compression during dilation of these veins can improve indicators of ANS dysfunction”. He calls this procedure Transvascular Autonomic Modulation (TVAM).

    This is not the standard definition of TVAM. Known definitions of TVAM encompass treating various diseases by introducing and activating therapeutic devices such as drug ports or electrodes into areas of the vasculature proximal to the target site of the autonomic nervous system. These TVAM therapies are configured to be continuous, such as sending electrical pulses to target sites in the CNS. The idea is to stimulate nerve fibers or other nuclei to optimize symptom suppression and minimize side-effects. Until Arata’s novel use of the interventional methodology described similarly as TVAM (that is, one-time balloonoplasty of the cervical veins), there was no such description or definition in the medical literature and a search reveals no other such association of cervical vein stimulation with a neurodegenerative disease. It would be highly unusual to expect a single treatment to act permanently on the symptoms of a disease, but this is what Arata claims happens.

    In Arata’s mind, this explanation of the association between neurovascular dysfunction and a neurodegenerative disease justifies continuation of venous angioplasty now that the CCSVI theory has been officially debunked in the major peer-reviewed journals. But the balloon angioplasty procedure is precisely the same as the 2,000 plus previous venous angioplasties performed on patients for a completely different reason (CCSVI). He has only added a manipulative procedure that does not provide evidence that it does anything to relieve MS symptoms in the intermediate or long-term. We note that this purportedly different procedure is performed for an unrecognized medical condition for which there is no evidence that it exists. But his new explanation for why venous angioplasty is now performed is quite different than the widely promoted reason where he previously explained ‘vascular dysfunction’ alone (CCSVI) as the certain cause of MS in the previous 2,000+ patients. In fact his explanation of ‘CCSVI as a cause of MS’ from 2011 through 2012 (the heyday of ‘liberation therapy’) is easily searchable on the internet despite Synergy’s recent attempt to change all website content to include TVAM…as if it was the only reason the clinic ever performed venous angioplasty for MS in the first place.

    So which one is it and what’s the truth? Why did he have to perform over 2,000 procedures on MS patients to discover a ‘new finding’ that coincided with the Lancet publication of Traboulsee’s discreditation of CCSVI (using ONLY 100 study patients in total)? We already know the truth and it seems more than a bit desperate. Arata is an Interventional Radiologist who has developed a lucrative niche market in medical tourism treating the veins of MS patients, mostly Canadians. This new, made-up disease that requires performing venous angioplasties on MS patients for a different reason today than in 2011, is a thinly-veiled attempt to save his dwindling specialized medical practice and to just continue doing what he always did, in the only area of medicine in which he specializes. So with his only tool as a hammer, naturally he is keen to see every problem as a nail. But in response to his research paper there has been no rush by other clinicians to follow up with investigations of their own; no acclaim that this is a breakthrough discovery, and no recognition of TVAM (his definition) as a reasonable therapeutic intervention for MS with lasting effect.

    Finally, Arata has neither attended nor presented his research to the International Society for Neurovascular Disease (ISNVD) at recent annual conferences despite many presentations on the subject of CCSVI by respected clinicians such as Robert Zivadinov, Paolo Zamboni, Marian Simka, Adnan Siddiqui, Mark Haacke, Aldo Bruno, Tomasz Ludyga, and Clive Beggs among others. These physicians are his colleagues who are genuinely interested in the CCSVI association with MS…but no Michael Arata despite his new and novel vascular therapy that he promotes as significant in its effect on MS as well as a host of other neurodegenerative diseases. The implication of his absence and failure to present his study to the conference alongside the presentations of these other noted figures in CCSVI research is that Arata’s own research isn’t really taken seriously by his colleagues. Indeed it’s pretty clear to everyone why he switched horses in midstream. That is, he is revenue-driven, not motivated at all by the quest for new medical discovery and the welfare of his patients. If he had been, data that could have informed us as to the safety and efficacy of venous angioplasty for MS would have come out of his 2,000 patient sample between 2010 and 2013 while he was performing venoplasties on MS patients at the rate of 3 or 4 per day. But none did. And in the end it was minimal data from a tiny 100 subject sample at UBC that trumped Arata’s claims. Upon publication of Traboulsee in the Lancet, he said nothing because he had no basis on which to argue despite the thousands of MS patients he had treated for CCSVI (many several times). At the time, the Synergy website claimed less than 10% rate of venous restenosis for their endovascular procedure which was a completely disingenuous claim, not backed up with any data whatsoever. By now, everyone reading this knows that most if not all MS patients, having had venous angioplasty, restenose at an average of about 90 days post-procedure and any healthful benefits seen immediately post-procedure cannot be maintained.

    I note that Arata did not present at the 2014 conference in San Francisco either, despite the fact that it was an international conference held in close proximity to his own clinic AND he had a new study, supposedly significant to the future of CCSVI. My guess is that he didn’t for the reasons stated here and that he wouldn’t want to get into a discussion of his practice with serious guys. Any claims about TVAM made by Synergy should be viewed not as medical innovation but as patient exploitation through medical tourism unless he can get other actual medical researchers (in the field of neurology, not radiology) to validate his research and endorse his conclusions.

    Will anyone who has seen significant improvement from their first, second, third or fourth endovascular treatment at Synergy whether called ‘CCSVI’ or ‘TVAM’, (or both) please respond so we can note that SOMEONE out of the thousands he has treated has seen improvement for more than a few months without regression back to symptoms?

    • Brian White says:

      Hi Stephen, a messed up autonomic system can easily lead to damage to the blood brain barrier. The autonomic nervous system is entirely responsible for contracting and expanding arteries in the brain to distribute the blood to promote correct oxygenation and cooling of the brain. Blood flow in the brain is very actively controlled and many of the veins in the brain can and do reverse flow depending on how the heat needs to be moved. The veins must have several alternative pathways to the heart available to properly cool the brain. Zenker in 1996 discovered this. So if it is working incorrectly, it might easily be causing a localized throbbing that can burst vessels or localized heating or de-oxygenation that could cause inflammation. Dr Arata recommends you get it right the first time with angioplasty because typically the second and 3rd time give little improvement. Jade’s nervous system came online one by one by one after the operation, it was just like the system was “rebooting”.

    • Lori Batchelor says:

      You included a quote from Dr. Doug Broeska, a fraudster who was competing for clients…hoping to make much more money with a much more dangerous procedure…? No credibility in my book. I did not get treated by Dr. Arata but I certainly would not hesitate to if I ever needed a “tune-up”! My venous angioplasty, done on March 17, 2011, is the only one I’ve had so far and ALL results have held–balance is now great, no-more drop-foot, no more heat-intolerance, no more headaches, no more erratic emotions–except my anger-intolerance flares when I see such negativity about the ONLY treatment that has EVER improved any of my symptoms attributed to MS.

      You mentioned Dr. Traboulsee–did you know that he is considering the possibility of vagus nerve stimulation as a possible explanation for the improvements many, including me, have seen? Dr. Traboulsee is in charge of an actual treatment trial in Vancouver, BC because he has records, including actual neurological testing, of more than 50% of patients, again including me, who have seen good results with angioplasty. Are you aware that the study you quote from the Lancet did not follow the correct protocol of Dr. Zamboni’s hypothesis?

      I’ve heard that ignorance is bliss but WILLFUL ignorance can spread much misinformation and harm–negativity certainly does show a closed mind!

      • Stephen Lovatt says:

        Lori, I posted my opinion on the article regarding Dr Arata’s (TVAM) treatment. It now appears that you have construed your own version of my opinion on the subject of CCSVI “Liberation Therapy”? I’m not sure who you have been in contact with when you state “you have been made more aware of my medical history”? Maybe you have consulted with my doctor? I would however hazard a guess that you have corresponded with some members of my expanding social media fan following.

        I will apologize for sharing the opinions of the accused fraudster “Henry Doug Broeska. Myself along with many others were not aware of what as recently been reported through the ” Free Press” uncovering his rather dubious, unsavory past. I also fell victim to his fraudulent scheme.

        I’m happy to hear that you and Denise along with a small percentage of other lucky patients world wide are still experiencing benefits from your treatments, irrelevant of where those treatments were received, following Zamboni’s procedure or not?. I have to date under gone the CCSVI Venoplasty treatment on three separate occasions. If I did not believe and hoped it to would have been some what effective, I most certainly would not of undergone the repeated procedures. In April of 2011, I traveled to Synergy. At that time to under go another one of Dr Arata’s novel “coined” procedures referred to as “Valve Breaking”. The long and short of it. A doctor Harris inflated a 20 mil balloon in my right internal jugular valve. This was carried out prior to either insufficient time for the amount of administer anesthetic to be effective or an insufficient dosage for this type of procedure? Whist I let out an agonizing scream for “deflation”, I heard a voice calling for more CC’s of something. It was obviously anesthetic because the left side dilation was carried out pain free. Dr Harris left the operating room, handed my wife a prescription, no post op follow up nothing. Not a word about my procedure to either me or my wife. We returned two days later for our scheduled appointment with a no show Dr Harris. We were just left with an embarrassed nurse, Dr Harris called me about a week and a half later for what it’s worth. There were also a lot more short comings involved with the entire experience nursing staff and administration.

        You referenced Dr Traboulsee’s trial, did he follow Dr Zamboni’s protocol? I have not read anything were he suggests patient benefits as a result of vagus nerve stimulation attributed to the CCSVI procedure. If he publishs an article or not we will have to wait and see. Though I seriously doubt he would condone the surgical process of inflating a balloon in a unrestricted vein in order to hand stimulate the nerve. The last I heard he claimed that he had in fact discovered 50% of healthy participants in his trial demonstrated constricted veins that can contribute to a diagnosis of what we have become to know as CCSVI.

        What I have learned over the past 4-5 years while pursuing alternate therapeutic relief for my MS, is to conduct as much diligence as you possibly can when searching. So we have come full circle and my original posted opinion of TVAM is still the same. With the addition of the following article.

        Home
        Food
        Drugs
        Medical Devices
        Radiation-Emitting Products
        Vaccines, Blood & Biologics
        Animal & Veterinary
        Cosmetics
        Tobacco Products

        Inspections, Compliance, Enforcement, and Criminal Investigations

        Print Share E-mail

        Home
        Inspections, Compliance, Enforcement, and Criminal Investigations
        Compliance Actions and Activities
        Warning Letters
        2012

        Compliance Actions and Activities

        Warning Letters

        2012

        Synergy Health Concepts, Inc 9/5/12

        Department of Health and Human Services logoDepartment of Health and Human Services
        Public Health Service
        Food and Drug Administration
        10903 New Hampshire Ave.
        Silver Spring, MD 20993-0002

        WARNING LETTER

        September 5, 2012

        VIA UNITED PARCEL SERVICE

        Michael A. Arata, M.D.
        President/Principal Investigator
        Synergy Health Concepts, Inc.
        P.O. Box 12139
        Newport Beach CA 92660

        Dear Dr. Arata:

        This Warning Letter is to inform you of objectionable conditions observed during the Food and Drug Administration (FDA) inspection conducted at Synergy Health Concepts, Inc. (Synergy Health) from April 10, 2012, to May 15, 2012, by an investigator from the FDA Los Angeles District Office. This inspection was conducted to determine whether activities by your firm as sponsor of the clinical studies: Venous Obstruction in Neurodegenerative Disorders Research Registry study (Registry study) and Radiographic and Intravascular (IVUS) Evaluation of Venous Morphology during CCSVI Treatment study (IVUS study), and your activities as clinical investigator of the IVUS study, complied with applicable federal regulations. The percutaneous transluminal angioplasty balloon dilation catheters and stents used in the Registry and IVUS studies are devices as that term is defined in section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h)], because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or function of the body. This letter also requests prompt corrective action to address the violations cited and discusses the written response dated June 5, 2012, to the noted violations.

        The inspection was conducted under a program designed to ensure that data and information contained in requests for Investigational Device Exemption (IDE), Premarket Approval (PMA) applications, and Premarket Notification submissions are scientifically valid and accurate. Another objective of the program is to ensure that human subjects are protected from undue hazard or risk during the course of scientific investigations.

        Our review of the inspection report prepared by the district office revealed several serious violations of Title 21, Code of Federal Regulations (CFR) Part 812-Investigational Device Exemptions, and Part 50-Protection of Human Subjects, which concerns requirements prescribed under section 520(g) of the Act, 21 U.S.C. § 360j(g). At the close of the inspection, the FDA investigator presented an inspectional observations Form FDA 483 for your review and discussed the observations listed on the form with you, John Joseph Hewett, M.D., Secretary and sub-investigator of the IVUS study, and Francis DeBarge-Igoe, RN, BSN, Practice Administrator. The deviations noted on the Form FDA 483, your written response, and our subsequent review of the inspection report, are discussed below:

        Synergy Health in its role as a sponsor:

        1. Failure to submit an application to the FDA and obtain IRB and FDA approval prior to allowing subjects to participate in an investigation [21 CFR 812.20, 21 CFR 812.40, and 21 CFR 812.42]

        A sponsor must submit an IDE application for a significant risk device to the FDA (21 CFR 812.40), and shall not begin an investigation, or part of an investigation, until an Institutional Review Board (IRB) and FDA have both approved the application or supplemental application relating to the investigation or part of an investigation (21 CFR 812.42). Your firm failed to adhere to the above-stated regulations. An example of your firm’s failure includes, but is not limited to, the following:

        Your firm failed to submit an IDE application to the FDA and to obtain FDA approval before allowing subjects to participate in the Registry and IVUS studies. These clinical research studies investigated the safety or effectiveness of angioplasty balloon devices and stents for percutaneous transluminal angioplasty for treating extracranial venous obstructive lesions and their influence on the clinical outcomes of multiple sclerosis patients. Investigating angioplasty balloon devices and stents through the Registry and IVUS studies to determine the safety or effectiveness of this unapproved and uncleared use constitutes an investigation under 21 CFR 812.2. Accordingly, the angioplasty balloon devices and stents are investigational devices. Because using these devices to investigate a treatment for extracranial venous obstructive lesions and its affect on multiple sclerosis patients presents a potential for serious risk to the health, safety, or welfare of the subjects, the devices are significant risk devices, as defined in 21 CFR 812.3(m). As a result, your firm must submit an IDE application to FDA to use the significant risk devices in an investigation, as required by 21 CFR 812.20. This helps ensure that the rights, safety, and welfare of human subjects are adequately protected and that the trial is conducted in a way that ensures the integrity of the clinical data.

        Your firm’s Registry study administered an investigational device for percutaneous transluminal angioplasty on at least (b)(4) subjects without submitting an IDE application to FDA and obtaining FDA approval (21 CFR 812.20).

        In addition, your firm’s IVUS study administered an investigational device for percutaneous transluminal angioplasty on at least (b)(4) human subjects without submitting an IDE application to FDA and obtaining FDA approval (21 CFR 812.20).

        Failure to furnish any notification or other material or information required by or under section 520(g) is a prohibited act under section 301(q)(1)(B) of the Act , 21 U.S.C. § 331(q)(1)(B).

        2. Failure to maintain accurate, complete, and current device shipment records [21 CFR 812.140(b)(2) and 21 CFR 812.140(d)].

        A sponsor is responsible for maintaining accurate, complete, and current records relating to the shipment and disposition of the devices. 21 CFR 812.140(b)(2). Such records shall include the name and address of the consignee, type and quantity of device, date of shipment, and batch number or code mark. Also, a sponsor is responsible for maintaining the records required by 21 CFR 812.140(b) during the investigation, for a period of 2 years after the date on which the investigation is terminated or completed, or the date that the records are no longer required for purposes of supporting a PMA application, whichever is later (21 CFR 812.140(d)). Specifically, your firm failed to maintain and could not produce during the inspection the device accountability records described above because, as noted in your (b)(4), affidavit, your firm is unable to (b)(4).

        These records are necessary to ensure that the use of investigational devices is consistent with the conduct of clinical research, limited to the investigational use, and traceable to individual subject exposure.

        As a clinical investigator:

        1. Failure to ensure that informed consent was obtained in accordance with 21 CFR Part 50 [21 CFR 50.27(a)].

        Informed consent shall be documented by the use of a written consent form approved by the IRB and signed and dated by the subject or the subject’s legally authorized representative at the time of consent. You failed to ensure that informed consent was obtained from subjects and documented in accordance with 21 CFR Parts 50 and 56. Specifically, in the IVUS study, you failed to use the IRB-approved written consent form dated (b)(4), for at least (b)(4) subjects and the IRB-approved written consent form dated (b)(4), for at least (b)(4) subjects.

        A valid informed consent process ensures that research subjects have a clear understanding of risks of participation in a research protocol, have sufficient opportunity to consider whether to participate in the study, and make an informed decision if they decide to participate.

        2. Failure to maintain accurate, complete, and current records related to your participation in the investigation [21 CFR 812.140(a)(2); 21 CFR 812.140(a)(3)(iii); and 21 CFR 812.140(d)].

        As a clinical investigator, you are responsible for maintaining accurate, complete, and current records of study-related matters, including receipt and use of devices that relate to the type and quantity, dates of receipt, batch number or code mark (21 CFR 812.140(a)(2)). You are also required to maintain records of each subject’s case history and exposure to the device (21 CFR 812.140(a)(3)(iii)). Also, a clinical investigator is responsible for maintaining the records required by 21 CFR 812.140(a) during the investigation, for a period of 2 years after the date on which the investigation is terminated or completed, or the date that the records are no longer required for purposes of supporting a PMA application, whichever is later (21 CFR 812.140(d)). Specifically, between (b)(4), and (b)(4), you failed to maintain and could not produce during the inspection the (b)(4) records, described above, in the IVUS study for at least (b)(4) subjects.

        These records are necessary to ensure and document that the use of investigational devices is limited to the clinical study and that subjects can be notified in the event of any need for additional follow-up, e.g., exposure to an unanticipated risk.

        Response to FDA Form 483:

        The response submitted June 5, 2012, on your behalf by C. Humphrey and Associates P.A., states that FDA has no jurisdiction to inspect or review Synergy Health’s studies. This is incorrect. The Registry and IVUS studies are subject to FDA jurisdiction because they involve the investigational use of medical devices by experts qualified by scientific training and experience to investigate the safety and effectiveness of such devices (see section 520(g) of the Act, 21 U.S.C. § 360j(g)). Synergy Health must apply for an IDE in accordance with the regulations in 21 CFR Part 812 to conduct these studies. The June 25, 2012 response is inadequate in that:

        1. it does not acknowledge that a clinical study of a significant risk device requires an IDE and FDA approval of the IDE before allowing subjects to participate, as required by 21 CFR 812.20 and 812.42;

        2. it does not acknowledge that clinical investigators must obtain and document informed consent using an IRB-approved informed consent document, as required by 21 CFR 50.27; and

        3. it does not address how you will correct the failure to maintain adequate device shipment records and the records related to your participation in these studies.

        The violations described above are not intended to be an all inclusive list of problems that may exist with your firm and your clinical study. It is your firm’s responsibility as a study sponsor; and you, as a clinical investigator, to ensure compliance with the Act and applicable regulations.

        Within 15 working days of receiving this letter, please provide documentation of the actions that your firm and you have taken or will take to correct these violations and to prevent the recurrence of similar violations in current or future studies for which your firm is the study sponsor and you are a clinical investigator. Any submitted corrective action plan must include projected completion dates for each action to be accomplished as well as a plan for monitoring the effectiveness of all corrective actions. Failure to respond to this letter and take appropriate corrective action could result in the FDA taking regulatory action without further notice to your firm or you.

        Your response should reference CTS – EC120258/E001 and be sent to:

        Attention: Anne T. Hawthorn
        Food and Drug Administration
        Center for Devices and Radiological Health
        Office of Compliance
        Division of Bioresearch Monitoring
        10903 New Hampshire Avenue
        Building 66, Room 3504
        Silver Spring, Maryland 20993-0002.

        A copy of this letter has been sent to FDA’s Los Angeles District Office, 19701 Fairchild, Irvine, CA 92612. Please send a copy of your response to that office.

        The Division of Bioresearch Monitoring has developed introductory training modules in FDA-regulated device clinical research practices, which are available on the FDA website. The modules are for persons involved in FDA-regulated device clinical research activities. These modules are located at the following website address: http://www.fda.gov/Training/CDRHLearn/ucm162015.htm.

        If you have any questions, please contact Anne T. Hawthorn at (301) 796-6561 or [email protected].

        Sincerely yours,
        /S/
        Steven D. Silverman
        Director
        Office of Compliance
        Center for Devices and
        Radiological Health

        cc:

        Holly Hunter Stull
        Chairperson
        Biomedical Research Institute of America
        (dba) BioMed IRB
        P. O. Box 600870
        San Diego, CA 92160-0870

        Page Last Updated: 01/29/2015
        Note: If you need help accessing information in different file formats, see Instructions for Downloading Viewers and Players.

        http://www.fda.gov/iceci/enforcementactions/warningletters/2012/ucm378832.htm

      • Stephen Lovatt says:

        Lori, I posted my opinion on the article regarding Dr Arata’s (TVAM) treatment. It now appears that you have construed your own version of my opinion on the subject of CCSVI “Liberation Therapy”? I’m not sure who you have been in contact with when you state “you have been made more aware of my medical history”? Maybe you have consulted with my doctor? I would however hazard a guess that you have corresponded with some members of my expanding social media fan following.

        I will apologize for sharing the opinions of the accused fraudster “Henry Doug Broeska. Myself along with many others were not aware of what as recently been reported through the ” Free Press” uncovering his rather dubious, unsavoury past. I also fell victim to his fraudulent scheme.

        I’m happy to hear that you and Denise along with a small percentage of other lucky patients world wide are still experiencing benefits from your treatments, irrelevant of where those treatments were received, following Zambonis procedure or not?. I have to date under gone the CCSVI Venoplasty treatment on three separate occasions. If I did not believe and hoped it to would have been some what effective, I most certainly would not of undergone the repeated procedures. In April of 2011, I travelled to Synergy. At that time to under go another one of Dr Arata’s novel “coined” procedures referred to as “Valve Breaking”. The long and short of it. A doctor Harris inflated a 20 mil balloon in my right internal jugular valve. This was carried out prior to either insufficient time for the amount of administer anaesthetic to be effective or an insufficient dosage for this type of procedure? Whist I let out an agonizing scream for “deflation”, I heard a voice calling for more CC’s of something. It was obviously anaesthetic because the left side dilation was carried out pain free. Dr Harris left the operating room, handed my wife a prescription, no post op follow up nothing. Not a word about my procedure to either me or my wife. We returned two days later for our scheduled appointment with a no show Dr Harris. We were just left with an embarrassed nurse, Dr Harris called me about a week and a half later for what it’s worth. There were also a lot more short comings involved with the entire experience nursing staff and administration.

        You referenced Dr Traboulsee’s trial, did he follow Dr Zamboni’s protocol? I have not read anything were he suggests patient benefits as a result of vagus nerve stimulation attributed to the CCSVI procedure. If he publishes an article or not we will have to wait and see. Though I seriously doubt he would condone the surgical process of inflating a balloon in a unrestricted vein in order to hand stimulate the nerve. The last I heard he claimed that he had in fact discovered 50% of healthy participants in his trial demonstrated constricted veins that can contribute to a diagnosis of what we have become to know as CCSVI.

        What I have learnt over the past 4-5 years while pursuing alternate therapeutic relief for my MS, is to conduct as much diligence as you possibly can when searching. So we have come full circle and my original posted opinion of TVAM is still the same. With the addition of the following article.
        Synergy Health Concepts, Inc 9/5/12http://www.fda.gov/iceci/enforcementactions/warningletters/2012/ucm378832.htm

    • Dan says:

      Stephen,

      Significant improvement? My wife was diagnosed with MS about 11 years ago, but has likely had it for over 20 years. Her condition was deteriorating, she walking or keeping her balance. If she got too warm on her treadmill (or in a bath) her vision simply shut down… she would become blind for about 20 minutes. She could no longer read books or newspapers and she was beginning to have real difficulty with memory and language. So, the CCSVI treatment was worth a shot. I have a well heeled sense of skepticism and was hopeful, but not optimistic.

      My wife’s vision “brightened” (her term) and returned to normal almost immediately after the treatment. She read magazines and newspapers for the next month. Her energy level ramped up over the next two weeks until she was her old self again. I could not keep her from enjoying our hot summers and she was back in the garden. We bought a hot tub for her to enjoy.

      The improvement was, and still is, significant. Whatever the real science, her results are real. Her illness was not psychosomatic and the results were not placebo. After almost five years, some of her symptoms have started to return, but she is still miles ahead of where she was before the procedure, so we are looking into another visit. It seems that the procedure may not benefit everyone, but it rescued my wife.

      Sorry it didn’t work out as well for you.

      Dan
      08/31/2015

      • Lori Batchelor says:

        Dan, I’m very happy to hear of your wife’s improvements. I always say it’s “worth a shot!” I am coming up to 4-1/2 years since treatment and all of my improvements are still holding. I have neurological testing/medical reports that agree it’s not psychological or placebo. I went from 6.5 to 4 on the EDSS scale even though I was NEVER supposed to improve with secondary/progressive MS. I’m sorry if it doesn’t work for everyone, like Stephen, but I am thrilled for myself and MANY others I have come to know about. Please give my best wishes to your wife.

        Lori

    • Marina says:

      Hi Stephen, I had the TVAM treatment with Michael Arata last February (I used to live in Canada).

      Symptoms gone:
      Lhermitte’s Sign
      Fingers/toes numbness and tingling

      Symptoms worse:
      Walking. Before the procedure I could walk miles; now I need to rest after walking a block. This really is alarming to me. After I told Arata repeatedly that I’ll see him in court, he and his secretary started ignoring me.

      • Stephen Lovatt says:

        Hi Marina,
        I`m sorry to hear of your deteriating health. CCSVI procedure is a somewhat safe and recognized procedure carried out in clinics world wide. TVAM on the other hand is an experimental procedure carried out solely at Synergy. You are not alone there are other patients who have experienced adverse reactions after receiving treatment. I`m quite surprised they have not been the subject of `Date Line`or `20/20` yet. You can contact me outside of this forum if you like. There is a lawyer specializing in these cases. Good luck, hope you start feeling better.

  6. Dagmar Lofts says:

    I am so glad you shared your story Lynn. CCSVI works in some cases and I think the doctors/researchers NEED to keep this in mind. Stem cells seems to be the new area and bonus if this helps more of us victims. I, like you Lynn, believe it is a vascular issue and we will see what future doctors discover.

  7. Denise Baillie says:

    On May 1, 2013 I Dr. Arata performed a TVAM treatment on me. My neurologist had changed my diagnosis to secondary progressive several months prior. I couldn’t walk without holding on to something and was barely able to get around even with my walker (to walk a block I would have to sit down at least 3 times to rest). I had been on Disability for four years and was ready to give up. Instead, I got treated and it was like someone flicked a switch from ‘sick’ to ‘healthy’. I was awake through the whole thing and when he treated my left side, I asked if someone had turned on another light because the room got brighter, and when he was treating my right side, I started crying because the headache I’d had non-stop for over 30 years just ‘dissolved’. The next day I was walking in the deep sand of the beach for more than an hour without even a cane! I haven’t needed any mobility aids since then and even bought myself a bicycle! I go hiking in the mountains again – and not just short ones! My neurologist at my last 2 visits has said my MS is now ‘stable’. Secondary Progressive MS is only supposed to get worse until it kills you; it is unheard of for Secondary-Progressive to become Stable! 99% of my symptoms were from dysautonomia, not my MS and are still completely gone more than 2 years later! While I believe just the CCSVI treatment would have helped me, at least short-term, I am absolutely convinced that I would not be doing nearly as well had I not also been given the TVAM treatment! Although the lights did seem to brighten as soon as he inflated the balloon on the left side, my 30-year headache didn’t go away until he was performing the TVAM treatment on my right side! Haters gonna hate, and doubters gonna doubt (Stephen Lovatt); but I KNOW the truth of how miraculous TVAM treatment can be, because I’m living it!

    • Stephen Lovatt says:

      I remember watching the video of you making a spectacle of yourself parading around the Alberta legislator. You may well in fact be an anomaly! I also clearly remember you leveling accusations against patients who posted positive testimonials, such as yours after receiving treatment from clinics that rivaled Dr Arata. They were “probably working for him” or “paid by him” rings a bell? But of coarse this would not apply in your case. I did not have a positive experience at Arata’s clinic, some still bear the scares of treatment with one paying the ultimate price. I will not keep my “sour grapes” you reference to myself, don’t like it don’t read it!

      • Brian White says:

        We went to California 2 years ago for angioplasty from Dr Arata for my wife. I was hopeful for some relief because I read up a lot about this and she seemed a good fit to be one of the lucky ones. It is one of the most astonishing things I have ever seen. She was disappointed because he told her it would not help her neuralgia but it helped just about every thing else. I took video before and after because people can look at the video and judge for themselves. Her right arm used to be cold like a zombie, it was warm again like a human the next day! It is absurd that this procedure is no longer carried out in Canada. 2 were done in Victoria BC where I live, in the exact same hospital where Jade had her stroke and nearly died. Both patients had successful outcomes but the BC medical board tried to fire the guy who helped the patients! The medical guys in charge of this file in British Columbia seem to have no moral compass at all. Jade still has her illness but a lot of symptoms are gone or greatly reduced. The video playlist can be found at https://www.youtube.com/watch?v=LcI9bTNGo1Q&list=PLkzXlmAwZTZfQ01RnN-8Ip5lUz0HrNWzN The evidence that this works is very very very clear. Brian

      • Lori Batchelor says:

        Stephen, I have been made more aware of your history and while I am sorry that you didn’t get the improvements you wanted from treatment for CCSVI, I am dismayed that you feel the need to be so negative. I have friends who also were 8.5 on the EDSS scale and they did not miraculously rise from their wheelchairs and do a dance–nobody should expect that from muscles that have atrophied for several years–but they don’t feel the need to put down everybody who had more success.

        I can tell you I have medical records confirming my diagnosis as confirmed secondary/progressive MS and that show I was 6.5 on the EDSS scale from at least 1996 until my angioplasty in March, 2011. I was NEVER supposed to improve but I did, becoming a 4 after my treatment. My neurologist was a naysayer and didn’t want me to have the treatment but when he saw my results he was very happy for me. You may be familiar with my before/after videos but in case you aren’t, here is the link to my 4-year angioversary video (it also includes links to a couple others including my examination by my neurologist where he says I am significantly better): https://www.youtube.com/watch?v=JdtDE93vrQ0&feature=youtu.be

        Nobody ever claimed treatment for CCSVI was a total cure but it sure has improved the quality of life for many–I would hope that you could have some understanding/compassion/happiness that many got some relief from this treatment when nothing else ever helped. MS sucks and if anything can help we should be allowed to try it if we want to!

  8. Lori says:

    Stephen Lovatt, I am aware of your history because you have posted it on many sites. While I agree TVAM is a “coined” term, it is still venous angioplasty. That is the same treatment for CCSVI–to improve fluid flow through occluded veins. I believe everybody deserves to be allowed to have proper flow and have been fighting for this right for people with MS in Canada but have been unsuccessful. Thus, medical tourism exists for venous angioplasty, TVAM, the liberation procedure…whatever you call it.

    I found this explanation of the MS Society-sponsored prevalence study “enlightening”, calling it “scientific misconduct” because it did NOT follow Zamboni’s protocol.
    http://ccsviinms.blogspot.ca/2014/12/scientific-misconduct.html
    so I’m not sure I’ll trust the results of the actual treatment trial, in progress, done by Traboulsee. Here’s an article that quotes him about the vagus nerve: “He admitted he didn’t know how CCSVI treatment might help, suggesting it might have to do with stimulation of vagus nerve”
    http://www.macleans.ca/society/life/ccsvi-scanning-study-finds-narrowed-veins-common-ccsvi-rare/

    I’m looking forward to the results of research from Italy and Australia due in 2016.

  9. Shannon says:

    I have been searching for ANYTHING that might help alleviate some of the symptoms. I have looked at HSCT in Mexico and fetal stemcell treatment and tvam. Tvam is about 1/4 of the cost of the other two. The other 2 claim both in writing and verbally on the phone to ‘cure and reverse’ MS….tvam claims to help alleviate some symptoms.
    TVAM seems more realistic to me.

    • Brian White says:

      Hi, Shannon, Tvam helps lots of people. And Dr Arata does not call it a cure. If you are lucky enough to have the right type of MS, it probably can be a cure. But my feeling is that “MS” is perhaps at least 3 different diseases with the same symptoms. Some of those diseases are of the nerves, and some are of the veins. Dr Arata has just found a research paper from 1998, which showed way back then that a sizable portion of “MS” sufferers had autonomic problems. Dr Arata has believed that balloon venoplasty accidentally treats this autonomic system problem for several years now. He thinks it does something to a poorly working vagus nerve or that the venoplasty activates stretch receptor nerves around the veins.(That have somehow been asleep or that have not been sending signals back to the brain as they should. If you imagine the autonomic nervous system as a big computer that directs blood to all the organs of the body, these signals are really important. “As soon as the balloon is expanded” many people get instant relief. This could be because the brain has been waiting (for years!) for those stretch receptors to send a signal. Suddenly, finally, that last cog is working and blood is going where it should go in the right amounts! Best of luck. Brian http://www.ncbi.nlm.nih.gov/pubmed/9517857

  10. Jj says:

    Brian, you seem very informed. I have head PRESSURE (not a headACHE) which gets worse from heat, stuffy room, closed Windows or steam.
    It’s constant, doesn’t go away- for a yr a half now.
    It was much more subtle at first.
    It intensified with time.
    A decent nights sleep brings the intensity down a bit but any activity such as standing a bit, or leaning a bit to wash blender intensifies the pressure.
    When intensified I feel hot esp. in neck/head, dizzy and feel faint.
    If It’s bad and I stand my head THROBES it’s then hard to breath my heart races and I feel faint.
    Often my head feels tense.
    Is this the throbbing and deoxygenization you posted of?
    Have you heard of this?

  11. Jj says:

    I saw Dr Arata, he said I have Dysautonomia.
    He won’t do the procedure saying I’m not well enough.
    He wants me to get my sleep improved first.
    Also said I’m older so procedure may not do as much- I’m 37….
    Really???
    He said it works better on teenagers but won’t do it on them for liability issues???
    Plenty of surgery is done on kids in hospitals, why is this different?
    He said he would dilate even if there’s no compression – I understand all that, but why am I not well enough when fatigue, sleeplessness are the norm for Dysautonomia..?

  12. Jj says:

    I have read of a couple ppl who had head PRESSURE and it was gone shortly after having TVAM.
    It’s not a headache as in migraine or splitting headache that come and go and ache.
    Pressure is a tension, a squeezing sensation (esp in between the eyes behind the nose and throughout the head- not at all a sinus issue so save those comments) that doesn’t go away – it’s constant, gets worse if bend over, even lean over, or if I tilt my head down and esp. Up.
    If I tilt head up or down enough I will feel dizzy, hot, out of breath, heart races and feel faint.
    I am bedridden can’t stand or sit for long before feeling faint.
    Anyone experience this?

Leave a Comment

Your email address will not be published. Required fields are marked *