Trial of Metformin-Clemastine Combo Enrolls First Patient
The first participant has been enrolled in a new clinical trial that is testing whether an antihistamine in combination with a diabetes medication might promote the repair of the myelin sheath in people with multiple sclerosis (MS).
The trial’s first participant, Annabelle, was diagnosed with relapsing MS over a decade ago.
“I was so inspired when I saw the clinical trial and signed up straight away… just a few months ago I was told there was nothing I could do — now I’m the first participant on a new trial! It’s given me so much hope,” Annabelle said in a press release from the U.K.’s MS Society.
“The recruitment of our first participant is a huge milestone. We’re another step closer to a time where a person with MS will be given a handful of treatments to tackle all the different elements of MS, so that their life will be minimally affected by the condition,” added Alasdair Coles, a professor at the University of Cambridge who is leading the trial.
MS is caused by the body’s immune system accidentally attacking the myelin sheath, which is a fatty covering around nerve fibers that helps them send electrical signals more efficiently.
There are more than a dozen disease-modifying therapies (DMTs) approved to treat relapsing types of MS. These medications all work to reduce the autoimmune inflammatory attack that drives the disease, thus decreasing relapse risk and slowing disability progression.
Although some existing DMTs can slow the progression of MS, they cannot repair damage that already has occurred. Repairing lost myelin — remyelination — is seen by many as a “holy grail” quest for MS treatment.
This Phase 2 clinical trial (NCT05131828), sponsored by the Cambridge University Hospitals NHS Foundation Trust, aims to enroll about 50 adults, ages 25 to 50, with relapsing-remitting MS who currently are on stable treatment with a DMT.
In addition to continuing their DMTs, participants will be assigned randomly to take a combination of metformin (500 mg) and clemastine (1.34 mg), or a placebo, by mouth once daily.
Metformin is a medication that is used to control blood sugar in people with diabetes. Research done in preclinical models has suggested that it may improve cognition and promote remyelination, but metformin has never been studied formally in MS.
Clemastine is an antihistamine that has been used to control allergies, and research has indicated that it can activate oligodendrocyte progenitor cells, a type of brain cell involved in the production of myelin.
A previous study, the Phase 2 ReBUILD trial (NCT02040298), tested clemastine in addition to DMTs in 50 MS patients with chronic damage to the optic nerve, which transmits signals from the eyes to the brain)
Results suggested that clemastine treatment improved the speed of signals along the optic nerves, and that this effect persisted for at least two months after stopping the therapy. Since a functional myelin sheath is crucial for neurons to efficiently and speedily send electrical signals, the results indicated that the therapy promoted remyelination.
Animal studies suggest that metformin may enhance the effects of clemastine, but the combination has never before been tested in humans.
The new study is currently enrolling participants with a delayed response to stimulus in at least one eye, but without a history of optic neuritis (inflammation of the optic nerve) in the past two years. Enrollment is ongoing at Addenbrooke’s Hospital in Cambridge, U.K.
The trial’s main goal is to compare the effect of the double treatment against a placebo on the speed of signals along the affected optic nerve after 26 weeks (about half a year). Changes in vision, retinal thickness, and MRI-based measures of myelin damage and repair also will be assessed.
“While there are over a dozen licensed treatments for people with relapsing forms of MS, there are still lots of people without treatment. This new research really is a major milestone in our plan to stop MS and we’re excited to get the results,” said Clare Walton, PhD, the MS Society’s head of research.