UCL Queen Square Institute of Neurology


First "3 IN 1" Multiple Sclerosis (MS) trial completed

12 October 2018

Researchers have completed a clinical trial on MS in which 3 different drugs were tested at the same time instead of 1 by 1 by 1: a world first in progressive neurological disease research

The ‘multi-arm’ study meant that tests for all 3 drugs could be completed in 5 years instead of around 15 – the time it would have taken if trialled individually under usual practice – and carried out at much less cost.

Designing a trial with multiple drugs is a complex statistical exercise, despite it being a simple concept, which is why it hasn’t been done before in MS. The 3 drugs in this study were not found to be effective – but researchers said the trial has broken new ground and established a benchmark for future trials not only for MS but also other neurodegenerative disorders such as the Dementias.

Funded by a partnership between the Medical Research Council and the National Institute for Health Research and MS Society UK and National MS Society (US), the ‘MS-SMART’ trial, taking place at a number of UK sites including UCLH, tested the safety and efficacy of 3 repurposed drugs (used to treat other conditions) in 445 people with secondary progressive MS – a later stage and currently untreatable form of the condition. All three drugs had been selected based on promising effects in experimental and pilot human studies.

Participants took amiloride (used to treat heart disease), riluzole (a treatment for motor neurone disease), fluoxetine (used for depression) or a placebo pill for two years. MRI scans and other clinical measures – such as walking, eyesight and simple thinking tests – were done before and after treatment to test for signs of MS disease progression. Researchers found no clinical effect of the 3 drugs being tested.

Professor Jeremy Chataway, Consultant Neurologist and lead researcher on the trial, based at UCL Queen Square Institute of Neurology who announced the trial results at a major European MS conference on Friday, said: “While we are disappointed with the result, this study improves our chances of success in the future. We have shown we can run faster trials, which will speed up the development of new treatments. It will also significantly improve our understanding of the biology of progression.”
Professor Siddharthan Chandran, Clinical Neurologist and a lead researcher at the University of Edinburgh, which was involved in the study, said: “Unfortunately these 3 drugs aren’t the right ones for progressive MS, but we will ramp up our efforts to find treatments for progressive neurological conditions, and we are confident we will succeed.”
Dr Susan Kohlhaas, MS Society Director of Research, says: “We know this is extremely disappointing for people with progressive MS and everyone involved with the trial – but we’ve learned a huge amount from the results. We’re now far better placed to rule out drugs that won’t work and to find ones that do more quickly. There are over 100,000 people living with MS in the UK and the community remains dedicated to finding effective treatments to fight this condition. We believe that, with the right investment, we can stop MS.”

MS is a neurological condition where the immune system attacks myelin, a substance surrounding the nerves, which leads to delay and confusion in messages sent from the brain and spinal cord to parts of the body. It affects almost three times as many women as men and it’s an unpredictable condition which can leave people with MS unable to move.

Symptoms can include chronic pain, muscle spasm, problems with walking, balance, speech, vision and extreme fatigue; there are over 100,000 people with MS in the UK but currently no treatments which impact on progression.

The research team and funders would like to thank all the participants and their families for their time, commitment and energy in taking part in the MS-SMART trial.

The team would also like to thank all the investigators and trial centres around the UK for being part of this fantastic project and making it happen.