Treatment of fatigue with methylphenidate, modafinil and amantadine in multiple sclerosis (TRIUMPHANT-MS): Study design for a pragmatic, randomized, double-blind, crossover clinical trial

Contemp Clin Trials. 2018 Jan:64:67-76. doi: 10.1016/j.cct.2017.11.005. Epub 2017 Nov 4.

Abstract

Background: Fatigue is the most common symptom of multiple sclerosis (MS). Amantadine, modafinil and amphetamine-like stimulants are commonly used in clinical practice for treatment of fatigue; however, the evidence supporting their effectiveness is sparse and conflicting.

Objective: To describe the design of a trial study funded by Patient-Centered Outcome Research Institute (PCORI) that will compare the efficacy of commonly used fatigue medications in patients with MS.

Design/methods: The study is a randomized, placebo-controlled, crossover, four-sequence, four-period, double-blind, multicenter trial of three commonly used medications for the treatment of MS-related fatigue (amantadine, modafinil, methylphenidate) versus placebo in fatigued subjects with MS. Adult patients with MS, with an Expanded Disability Status Scale of <7.0 are eligible to participate. Participants will be randomized to one of four predefined sequences of medication administration. Each sequence comprises four 6-week periods of treatment with one of the 3 study drugs or placebo, and three 2-week washout periods between medication periods.

Results: 136 participants will be randomized over two years in two academic centers in the United States starting in the Summer 2017. Complete enrollment is expected by early 2019. The primary outcome of the study is the modified fatigue impact scale (MFIS) score while participants receive the maximally tolerated dose of each study medication (or placebo). Safety and tolerability of the medications and heterogeneity of treatment effect will also be assessed.

Conclusions: Results of the proposed study will provide evidence-based and personalized treatment options for patients affected by MS-related fatigue. Clinicaltrials.gov registration number: NCT03185065.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Amantadine / therapeutic use
  • Central Nervous System Stimulants / therapeutic use*
  • Cross-Over Studies
  • Double-Blind Method
  • Fatigue / drug therapy*
  • Fatigue / etiology*
  • Humans
  • Methylphenidate / therapeutic use
  • Modafinil / therapeutic use
  • Multiple Sclerosis / complications*
  • Research Design*

Substances

  • Central Nervous System Stimulants
  • Methylphenidate
  • Amantadine
  • Modafinil

Associated data

  • ClinicalTrials.gov/NCT03185065