Do Neuroprotective Drugs Affect Brain Volume in Patients With Secondary Progressive MS?

Amiloride, fluoxetine, and riluzole do not have an effect on percentage brain volume change (PBVC) among patients with secondary progressive multiple sclerosis (MS), according to results of a new trial.

“The absence of evidence for neuroprotection in this adequately powered trial indicates that exclusively targeting these aspects of axonal pathobiology in patients with secondary progressive [MS] is insufficient to mitigate neuroaxonal loss,” the researchers wrote.

Based on preclinical and clinical research, the study authors identified 3 neuroprotective drugs that act on different axonal pathobiologies. The drugs’ efficacy was evaluated through a phase 2b trial that was conducted at 13 clinical neuroscience centers in the United Kingdom.

Between January 29, 2015, and June 22, 2016, 445 patients aged 25 to 65 years with secondary progressive MS were randomly assigned to receive twice-daily amiloride, 5 mg (n=111); fluoxetine, 20 mg (n=111); riluzole, 50 mg (n=111); or placebo (n=112). The patients—who all had an Expanded Disability Status Scale score of 4.0 to 6.5—followed their respective treatments for 96 weeks.

In all, 393 participants were included in the primary analysis of volumetric magnetic resonance imaging (MRI) PBVC from baseline to 96 weeks. Of these participants, 99 were from the amiloride group, 96 were from the fluoxetine group, 99 were from the riluzole group, and 99 were from the placebo group.

The researchers found no difference between any active treatment and placebo in PBVC at week 96. No emergent safety issues were reported either. 

The incidence of serious adverse events was low and similar across study groups, with the most common serious adverse events being infections and infestations. The 3 deaths that occurred during the study were unrelated to active treatment. 

“These findings argue for investigation of different mechanistic targets and future consideration of combination treatment trials,” the researchers concluded. “This trial provides a template for future simultaneous testing of multiple disease-modifying medicines in neurological medicine.”

—Colleen Murphy


Chataway J, De Angelis F, Connick P, et al; MS-SMART Investigators. Efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis (MS-SMART): a phase 2b, multiarm, double-blind, randomised placebo-controlled trial. Lancet Neurol. 2020;19(3):214-225.