Octopus mega-trial opens to progressive MS patients in the UK

The study is billed as the first ever 'multi-arm, multistage' trial for MS

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by Steve Bryson, PhD |

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The world’s first mega-trial is recruiting people in the U.K. with progressive forms of multiple sclerosis (MS) to investigate the effectiveness of several approved therapies — at the same time.

Named Octopus for its various arms, the study, which is expected to enroll at least 1,200 participants over the next six years, will evaluate multiple treatments with the potential to accelerate their development three times faster than separate trials would. Anyone with primary progressive MS (PPMS) or secondary progressive MS (SPMS) living in the U.K. can register their interest at the UK MS Register, according to a news release from the U.K.’s MS Society, which is funding the trial.

Recruitment is now ongoing at the University College London Hospitals (UCLH), with additional confirmed sites yet to open in Belfast, Edinburgh, Cardiff, Coventry, Leeds, and Southampton.

Octopus, which is led by scientists at the Queen Square MS Centre and the Medical Research Council (MRC) Clinical Trials Unit at UCL, will eventually open in up to 30 sites around the U.K., including Scotland, Wales, Northern Ireland, Yorkshire, the West Midlands, and the south of England.

“Launching the world’s first multi-arm, multistage trial for MS has long been an ambition of ours and opening the doors to Octopus is a momentous milestone,” said Emma Gray, PhD, assistant director of research at the MS Society.

One of the first participants to enroll was Ailsa Guidi, 47, a medically retired mother of three who was diagnosed with relapsing-remitting MS (RRMS) at 24 and whose disease recently progressed to SPMS.

“There are two treatments available that can help some people with secondary progressive MS, but I’m sadly not eligible for them,” Guidi told the MS Society. “I’m a positive person, but facing progressive MS feels quite different from living with the relapsing form.”

“After being accepted last month, I feel excited that I’m joining a long line of people who have helped progress MS research,” Guidi added. “Octopus has the potential to find treatments for people, like me, living with progressive MS – it’s given me hope.”

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Making available more treatments for progressive MS

Octopus will test several experimental MS therapies against a shared control group. Treatments that appear effective from early data can continue into the next stage without needing to set up a new trial and new infrastructures.

In Octopus, the earliest assessments will be done with MRI scans, so researchers can see if the drug is slowing brain atrophy, loss of myelin, and other measures of decline, compared with a placebo. Because these changes usually occur several months before overt signs of disability progression are evident, researchers can look for signs of efficacy much earlier.

If a drug shows promise in this first stage, it will move into the trial’s second stage, where disability progression will be assessed. Drugs that don’t show promise will be removed from the trial and a new treatment will be added.

“The multi-arm, multistage approach to trialing emerging medications has been utterly transformative in other conditions, so I’m thrilled we’re now able to apply it to progressive MS,” said Jeremy Chataway, PhD, a neurologist at UCLH and Octopus’ co-lead. “Ultimately, Octopus will lead to more treatments for progression becoming available to people living with MS sooner. I know our amazing community of people is poised to help us make it to the top, so we can find the answers we so desperately need.”

To find treatments for everyone with MS, we need trials to be as inclusive as possible and produce results much faster.

To identify potential therapeutics, a team of scientific and clinical specialists, alongside people with MS, reviewed and ranked existing drugs used in other conditions that might be able to protect nerves.

Metformin, approved for diabetes in the U.K., was selected because it has shown potential for boosting the repair of myelin, the fatty protective coating on nerve fibers that are damaged in MS. R/S alpha lipoic acid, approved in Germany for neuropathy (nerve damage), is the second therapy to be tested.

Because some versions of lipoic acid are available as unregulated supplements, meaning it’s not clear how they’re made or what they contain, patients using them may be excluded from Octopus.

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After registering an intent to join, people with MS will be asked about their disease and where they live to ensure an open site is nearby. They’ll then attend a screening visit to determine eligibility, which will include questions, blood tests, and MRI scans.

Enrolled participants will be assigned metformin, R/S alpha lipoic acid, or a placebo. Top-line data from the mega-trial reporting on treatment efficacy is expected by 2028 at the earliest.

“To find treatments for everyone with MS, we need trials to be as inclusive as possible and produce results much faster. This is what we want Octopus to achieve,” said Octopus co-lead Max Parmar, PhD, the director of the MRC Clinical Trials Unit at UCL. Parmar said he knew he was “up for the challenge” when he was asked by the MS Society to help set up one of the first multi-arm, multistage trials for a neurological condition.

The study is also supported by the National Institute for Health and Care Research UCLH Biomedical Research Centre.

“More than 130,000 people live with MS in the UK, and there are tens of thousands with progressive forms who have nothing to stop their MS getting worse,” Gray said. “By tapping into the potential of approved drugs, which may have the potential to protect nerves, we can develop new treatments for MS faster.”

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