Treatment of Fatigue With Methylphenidate, Modafinil and Amantadine in Multiple Sclerosis
- Conditions
- Fatigue in Multiple Sclerosis
- Interventions
- Registration Number
- NCT03185065
- Lead Sponsor
- Johns Hopkins University
- Brief 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 141
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Arm A Placebos amantadine, placebo, modafinil, methylphenidate Arm B Methylphenidate placebo, methylphenidate, amantadine, modafinil Arm A Methylphenidate amantadine, placebo, modafinil, methylphenidate Arm B Placebos placebo, methylphenidate, amantadine, modafinil Arm C Placebos modafinil, amantadine, methylphenidate, placebo Arm C Modafinil modafinil, amantadine, methylphenidate, placebo Arm D Modafinil methylphenidate, modafinil, placebo and amantadine Arm D Placebos methylphenidate, modafinil, placebo and amantadine Arm A Modafinil amantadine, placebo, modafinil, methylphenidate Arm A Amantadine amantadine, placebo, modafinil, methylphenidate Arm B Amantadine placebo, methylphenidate, amantadine, modafinil Arm B Modafinil placebo, methylphenidate, amantadine, modafinil Arm C Amantadine modafinil, amantadine, methylphenidate, placebo Arm C Methylphenidate modafinil, amantadine, methylphenidate, placebo Arm D Amantadine methylphenidate, modafinil, placebo and amantadine Arm D Methylphenidate methylphenidate, modafinil, placebo and amantadine
- Primary Outcome Measures
Name Time Method Modified Fatigue Impact Scale (MFIS) Score Week 5 of each treatment period MFIS score during the fifth week of treatment period. The total score of the MFIS ranges from 0 to 84. Higher scores denote more severe fatigue.
- Secondary Outcome Measures
Name Time Method Epworth Sleepiness Scale (ESS) Score Week 5 of each treatment period ESS score during the fifth week of treatment period. The ESS score can range from 0 to 24. The higher the score, the higher that person's average sleep propensity in daily life, or their 'daytime sleepiness'.
Quality of Life in Neurological Disorders (Neuro-QoL) Item Bank - Fatigue Score Week 5 of each treatment period Neuro-QoL Item Bank - Fatigue T score during the fifth week of treatment period. T-score distributions rescale raw scores into standardized scores with a mean of 50 and a standard deviation (SD) of 10. Higher T-scores denote more severe fatigue.
Trial Locations
- Locations (2)
University of California San Francisco
🇺🇸San Francisco, California, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States