MS-SMART stands for Multiple Sclerosis – Secondary progressive Multiple Arm Randomisation Trial. This trial for secondary progressive MS is testing three drugs at once:

  • amiloride - licensed to treat heart disease
  • fluoxetine - licensed to treat depression
  • riluzole - licensed to treat motor neurone disease (MND)

Current phase of trial: Phase 2

Type of MS: Secondary progressive MS

How do the MS-SMART drugs work?

All three drugs have been shown to have the potential to protect nerve cells in the brain and spinal cord from damage (known as neuroprotection). Neuroprotective treatments could slow or even halt the progression of MS.

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How are the MS-SMART drugs taken?

As a tablet that is taken orally.

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Latest research


This three-year trial will test the benefits of amiloride, fluoxetine and riluzole for 440 people with secondary progressive MS, compared to a placebo.

Participants will be divided into four groups. Each group takes one of the following for two years:

  • 5mg of amiloride twice daily
  • 50mg riluzole twice daily
  • 20mg fluoxetine twice daily
  • placebo

Researchers will use MRI scans to test if any of the drugs could protect nerves from damage in MS. They will do this by measuring if the drugs slow the rate of brain atrophy (shrinkage).

The trial is due to finish in 2018.

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Earlier research

In 2007, we set up the UK MS Clinical Trials Network (CTN): a group of MS experts tasked with developing and producing clinical trials for progressive MS. The group, funded by the MS Society, carried out £500,000 worth of underpinning research that was needed in order to develop the MS-SMART trial.

Through the work of the CTN, a number of drugs were established as having the potential to be neuroprotective, of which these three scored particularly highly. They are all in use for other conditions, have a good safety profile, and most importantly have shown promise in early phase clinical trials in people with MS.

Amiloride: one trial has tested the safety and effectiveness of amiloride in 14 people with primary progressive MS. The treatment was deemed safe, and a significant reduction in brain atrophy was observed.

Fluoxetine: two trials have tested fluoxetine as a treatment for people with MS (one for relapsing remitting and one for progressive MS). The progressive MS trial found fluoxetine to be safe, while the relapsing remitting MS trial (with 40 participants) found that fluoxetine reduced the number of lesions within the brain.

Riluzole: one uncontrolled pilot study has been carried out in 16 people with primary progressive MS. Results from this trial suggest that riluzole may be able to slow spinal cord atrophy and the development of new lesions within the brain.  

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What are the side effects of the MS-SMART drugs?

The side effects associated with these drugs in people with MS are currently unknown, although side effects reported in the early small stage trials include:

Amiloride: two out of 14 patients in a small trial stopped treatment, due to worsening bladder problems.

Fluoxetine: one heart attack was reported in the primary progressive trial (although researchers believe that this is unlikely to be related to the treatment), along with milder effects of drowsiness and fatigue at the start of treatment. In the relapsing remitting trial, nausea and drowsiness were reported at the start of treatment.

Riluzole: the pilot study reported no adverse effects.  

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How do the MS-SMART drugs compare with current therapies?

These drugs haven’t yet been directly compared with different therapies for the treatment of MS, so it isn’t possible to draw conclusions about their relative effectiveness.

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When are the MS-SMART drugs likely to become available?

Amiloride, fluoxetine and riluzole are already licenced for other conditions, but they’ll need to undergo a larger phase 3 trial to definitively test their effectiveness for people with MS.

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