NCT03185065

Treatment of Fatigue With Methylphenidate, Modafinil and Amantadine in Multiple Sclerosis

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 141 (actual)
• Sponsor: Johns Hopkins University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Randomized, placebo-controlled, crossover, 4-sequence, 4-period, double-blind (participants and investigators), multicenter trial of 3 commonly used medications for treatment of MS-related fatigue (amantadine, modafinil, methylphenidate) versus placebo in fatigued subjects with MS defined by McDonald Criteria.

Detailed description

This is a randomized, placebo-controlled, crossover, 4-sequence, 4-period, double-blind (participants and investigators), multicenter trial of 3 commonly used medications for treatment of MS-related fatigue (amantadine, modafinil, methylphenidate) versus placebo in fatigued subjects with MS defined by McDonald Criteria. Using a balanced Latin-square crossover design, subjects will be allocated, in a double-blind, randomized fashion, to one of the four treatment sequences (Figure 1): 1) amantadine, placebo, modafinil, methylphenidate; 2) placebo, methylphenidate, amantadine, modafinil; 3) modafinil, amantadine, methylphenidate, placebo; and 4) methylphenidate, modafinil, placebo and amantadine. Each medication will be titrated over four weeks to the participants' highest tolerated dose or the pre-defined highest dose. The dosing and titration schedule of the study medications are depicted in Figure 2. Each treatment period will be 6 weeks and there will be a 2-week washout period between each treatment period. At the beginning of the trial, a biostatistician at University of California, San Francisco (UCSF) will prepare a concealed allocation schedule, randomly assigning the four sequences, in blocks of 4, to a consecutive series of numbers and at the time of enrollment, each participant will be assigned the next consecutive number (and hence the sequence of study medications). The primary endpoint of the study will be fatigue severity as measured by the MFIS score, between 26th and 35th day of each treatment period (while the patient is taking the maximal tolerated or target dose). The MFIS is a validated patient-reported outcome. The questionnaire will be administered remotely (through internet, phone or mailed forms) and the participants can answer the questions in few minutes while at home or at their work place. The questionnaire has been validated in English and Spanish.

Conditions

• Fatigue in Multiple Sclerosis

Interventions

Type	Name	Description
DRUG	Amantadine	100 mg of amantadine increased to 200 mg of amantadine, if tolerated
DRUG	Modafinil	100 mg of modafinil increased to 200 mg of modafinil, if tolerated
DRUG	Methylphenidate	5 mg of methylphenidate uptitrated to max of 20 mg of methylphenidate, if tolerated
DRUG	Placebos	1 placebo capsule increased to max of 2 capsules twice daily

Timeline

• Start date: 2017-10-04
• Primary completion: 2019-11-21
• Completion: 2019-11-21
• First posted: 2017-06-14
• Last updated: 2020-10-20
• Results posted: 2020-10-19

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study