MS-SMART stands for Multiple Sclerosis – Secondary progressive Multiple Arm Randomisation Trial. This trial for secondary progressive MS is testing 3 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?
- How are the MS-SMART drugs taken?
- Latest research
- Earlier research
- What are the side effects of the MS-SMART drugs?
- How do the MS-SMART drugs compare with current therapies?
- When are the MS-SMART drugs likely to become available?
All 3 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.
As a tablet that is taken orally.
The MS-SMART trial
This 3-year phase 2 trial is currently recruiting. The trial aims to test the effectiveness of amiloride, fluoxetine and riluzole in 440 people with secondary progressive MS, compared to a placebo.
Participants will be divided into 4 groups, receiving one of the following for 96 weeks: 5mg of amiloride twice daily; 50mg riluzole twice daily; 20mg fluoxetine twice daily; or a placebo.
Through MRI scans, the researchers will compare the rate of brain atrophy (shrinkage) that normally occurs in secondary progressive MS in each of the 4 groups. This change in brain size will be the primary measurement for testing the effectiveness of each drug.
In 2007, the MS Society 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 3 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: 2 trials have tested fluoxetine as a treatment for people with MS (one for relapsing remitting and one for progressive MS). In 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.
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: 2 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.
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.
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 in MS.
Research is still at an early stage and it will be a few years before we know whether any of these drugs are effective treatments for people with MS.