“While these results are disappointing, we can learn a lot from well-controlled clinical trials like MS-SMART that will help fuel new approaches for finding desperately needed solutions for people living with progressive forms of MS,” said Bruce Bebo, PhD, Executive Vice President, Research, at the National MS Society. “Learnings from this study and others will help inform the Society’s research priorities and those of other research funders like the International
Progressive MS Alliance.”
Background: There are few therapies that have shown benefits for people living with secondary progressive multiple sclerosis, a stage of MS that follows an initial relapsing-remitting course in which there is a progressive worsening of neurologic function and accumulation of disability over time. Because progression usually occurs over many years, there is a need for innovative clinical trial designs that can more quickly test therapies for their potential to protect the nervous system from harm and slow or stop progression.
Dr. Jeremy Chataway (University College London) and colleagues set out to conduct an innovative, multi-arm trial that would permit testing of three oral drugs at the same time, all of which had shown promising neuroprotective properties. Amiloride is a drug that reduces the influx of calcium and sodium into cells and is used to treat high blood pressure; fluoxetine is a treatment for depression that increases production of a chemical that may have beneficial effects on brain cells; and riluzole is a treatment for ALS (motor neuron disease) that blocks glutamate, a neurotransmitter that may build up and cause nerve cell damage. Each of these are approved by the U.S. Food and Drug Administration for other conditions.
The Trial: A total of 445 individuals in the United Kingdom with secondary progressive MS were enrolled in the 96-week trial. Each was randomly assigned to receive amiloride, fluoxetine, riluzole, or placebo, and the participants and healthcare professionals were not aware of their assignment. The main outcome measure was percentage brain volume change from the beginning of the study to the end, measured with MRI imaging. Additional outcomes were measured, including numbers of new or enlarging MS brain lesions; cognitive tests; physician and patient perceptions of effectiveness; and confirmation of whether the multi-arm strategy was successful.
Results: At 96 weeks, none of the drugs showed evidence of slowing brain atrophy or other significant benefits. However, the results confirm the feasibility of this innovative multi-arm phase 2 trial design, which in the future will likely enable much quicker assessments of potential therapies for progressive MS.
Dr. Chataway reported results on October 12, 2018 at the meeting of the European Committee for Treatment and Research into Multiple Sclerosis (ECTRIMS) in Berlin. The clinical trial was investigator-initiated and funded by University College London and multiple other sponsors and agencies including the UK Multiple Sclerosis Society and the National Multiple Sclerosis Society (USA). Other sponsors included the University College London, the Efficacy and Mechanism Evaluation Programme, Medical Research Council, and managed by the National Institute for Health Research.
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