- First time a multi-arm, multi-stage (MAMS) trial has reported positive results in a neurological condition
- Diabetes drug metformin removed from trial, but innovative design means more drugs can be added in 2027
- Researcher warns of significant risk of taking unlicensed drugs outside the safety of a clinical trial
Interim results from a world-first multiple sclerosis (MS) trial have found that an existing medication, alpha-lipoic acid (also known as ALA), is showing early promise as a potential treatment to slow progression in MS.
Researchers from the Queen Square MS Centre and Innovative Clinical Trials Unit (InCTU) at University College London (UCL) revealed that the drug could have potential to become the first neuroprotective treatment in MS. But stress people should not attempt to acquire alpha-lipoic acid outside a clinical trial, as further research is needed to fully understand its efficacy – and particularly its safety – in MS.
MS can be debilitating, exhausting, and unpredictable, and symptoms range from chronic fatigue and bladder and bowel problems to mobility difficulties. While there are over a dozen treatments for those living with relapsing MS, tens of thousands with the progressive form* desperately need treatments to stop their MS getting worse. Those drugs that do exist only work on one aspect of the condition – the immune system. They don’t stop the gradual nerve damage that leads to long-term disability. Finding ways to protect nerves from damage is key.
The innovative progressive MS trial, Octopus, uses a multi-arm multi-stage (MAMS) design, which means it can test potential new treatments up to three times faster than conventional trials.
Supported by the National Institute for Health and Care Research Biomedical Research Centre: UCLH, Octopus has provided a blueprint for similar trials across neurological conditions, from motor neuron disease and Parkinson’s disease to psychosis. It has been testing two drugs at once – a high dose of alpha-lipoic acid and diabetes drug, metformin – and comparing each one against a placebo.
Alpha-lipoic acid will now continue to the second stage of the trial. Data from both stages will then be combined to provide a definitive phase 3 result. However, metformin did not demonstrate sufficient promise to be taken forward. This will now be removed from the trial, with all participants from that arm leaving the trial and coming off the drug in the coming weeks.
More than 850 people have joined the trial at hospitals across the UK, including Scotland, as well as in Australia1. Now the team are seeking hundreds more people living with primary or secondary progressive MS to sign up.
Thanks to this positive result, in the coming years Octopus will become the world’s largest ever trial in progressive MS. The trial design means other drugs could be added as soon as early 2027.
Margaret Anderson, 57, lives in North Edinburgh and joined the Octopus trial after it launched in the city. She was diagnosed with relapsing remitting MS about 20 years ago and now lives with the secondary progressive form of the condition. Her symptoms include fatigue, spasms, sensory pain, and mobility issues, and she uses crutches to help her walk.
After finding out she would be continuing on the trial, Margaret said: “It makes me feel optimistic for the future knowing there’s research like the Octopus trial happening. There must have been some good signs with the drug they’ve carried on so there’s hope there.
“I heard about the trial from my neurologist, and I wanted to take part because us patients have to do our bit as well. It might not benefit me but if it can benefit people with MS in the future then I’ll do anything I can. You don’t know whether you’re on a drug or a placebo but it’s a chance worth taking.”
When asked what she would say to someone living with MS who was considering registering their interest in Octopus or another research trial, Margaret added: “I’m being very, very well looked after and cared for on this trial. I would tell people not to be afraid of signing up.
“The more of us that can take part in research the better, and the more the researchers will learn. And hopefully, as well as finding new treatments, one day there’ll be a cure for MS.”
Dr Peter Foley is Principal Investigator for Octopus at the Edinburgh trial site, based at the Anne Rowling Regenerative Neurology Clinic at the University of Edinburgh. He said: “The team at the Anne Rowling Clinic has been encouraged to hear of the latest developments in the Octopus trial.
“While of course it’s disappointing in some ways that metformin won’t progress to the next stage of the trial, it’s positive that Octopus is already helping to work out what treatments might be helpful.
“Building on these early results, alpha-lipoic acid will continue to be tested as a potential future treatment for progressive MS. We’re happy to be able to support delivering this important trial in Scotland, and are very grateful to all the trial participants who have committed so much time and effort.
“We hope that the success of the innovative Octopus trial design so far is a positive step towards developing effective therapies for people affected by progressive MS.”
Octopus is being led by leading UCL neurologist Professor Jeremy Chataway, whose vision to rethink trials for progressive MS was born over a decade ago. He says: “This is very exciting and proves not only that the Octopus trial design works, but that a new way of protecting nerves could be on the horizon.
“Of course, learning that metformin will be discontinued is disappointing. But finding treatments for progressive MS is extremely difficult, and we’re so pleased to be taking alpha-lipoic acid into the second stage of the trial.
“We’re now looking forward not only to seeing what the final results are, but also to adding in new ‘arms’ to Octopus next year.
“In the meantime, we do need to remind people with MS to not try to source unproven drugs outside the safety of a clinical trial.”
Dr Emma Gray, Director of Research at the MS Society, says: “We are so proud to be funding the first ever MAMs trial for people with progressive MS. It’s been a privilege to be part of the team and to have united the MS research community and worked with people living with MS to make this happen.
“MS can be debilitating, exhausting and unpredictable but today’s results are a huge step forward and show treatments to slow or stop MS progression have never been more within our reach. Octopus was made possible entirely by public donations and our Stop MS Appeal.
“We’re continuing to seek funding from our generous supporters for the future delivery of the trial to build a future where no one needs to worry about MS getting worse.”
Professor Max Parmar is Professor of Medical Statistics and Epidemiology and Director of the Institute of Clinical Trials and Methodology at UCL. His underpinning work was key to the launch of the STAMPEDE trial for prostate cancer in 2005 – the world’s first MAMS Platform trial for any condition and the inspiration behind Octopus.
He says:”The MAMS platform design has transformed how we test new treatments in prostate cancer through the STAMPEDE trial, dramatically accelerating the evaluation of promising therapies and delivering benefits to patients years, and in some cases decades, sooner than would have been possible with conventional approaches.
“It has fundamentally changed the pace at which we can make progress. It is therefore tremendously encouraging to see these interim results from Octopus, demonstrating for the first time that this innovative approach can be successfully applied in multiple sclerosis. The potential to evaluate treatments more efficiently and accelerate progress for people living with MS is incredibly exciting.
“Reaching this stage is a remarkable achievement and reflects the vision, dedication and collaboration of the entire MS research community, as well as the commitment of the participants who have made the trial possible. I am excited to see how Octopus develops and the impact it could have on the future of MS treatment research.”
Anyone who has primary or secondary progressive MS and is aged between 25 and 70 in the UK can register their interest via the UK MS Register to take part in stage 2 of the Octopus trial.
Please note there is a waiting list for the trial.
Visit www.ukmsregister.org/octopus.
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