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Treatment of Fatigue With Methylphenidate, Modafinil and Amantadine in Multiple Sclerosis (TRIUMPHANT-MS)

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ClinicalTrials.gov Identifier: NCT03185065
Recruitment Status : Completed
First Posted : June 14, 2017
Results First Posted : October 19, 2020
Last Update Posted : October 20, 2020
Sponsor:
Collaborator:
Patient-Centered Outcomes Research Institute
Information provided by (Responsible Party):
Johns Hopkins University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Fatigue in Multiple Sclerosis
Interventions Drug: Amantadine
Drug: Modafinil
Drug: Methylphenidate
Drug: Placebos
Enrollment 141
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm A Arm B Arm C Arm D
Hide Arm/Group Description

amantadine, placebo, modafinil, methylphenidate

Amantadine: 100 mg of amantadine increased to 200 mg of amantadine, if tolerated

Modafinil: 100 mg of modafinil increased to 200 mg of modafinil, if tolerated

Methylphenidate: 5 mg of methylphenidate uptitrated to max of 20 mg of methylphenidate, if tolerated

Placebos: 1 placebo capsule increased to max of 2 capsules twice daily

placebo, methylphenidate, amantadine, modafinil

Amantadine: 100 mg of amantadine increased to 200 mg of amantadine, if tolerated

Modafinil: 100 mg of modafinil increased to 200 mg of modafinil, if tolerated

Methylphenidate: 5 mg of methylphenidate uptitrated to max of 20 mg of methylphenidate, if tolerated

Placebos: 1 placebo capsule increased to max of 2 capsules twice daily

modafinil, amantadine, methylphenidate, placebo

Amantadine: 100 mg of amantadine increased to 200 mg of amantadine, if tolerated

Modafinil: 100 mg of modafinil increased to 200 mg of modafinil, if tolerated

Methylphenidate: 5 mg of methylphenidate uptitrated to max of 20 mg of methylphenidate, if tolerated

Placebos: 1 placebo capsule increased to max of 2 capsules twice daily

methylphenidate, modafinil, placebo and amantadine

Amantadine: 100 mg of amantadine increased to 200 mg of amantadine, if tolerated

Modafinil: 100 mg of modafinil increased to 200 mg of modafinil, if tolerated

Methylphenidate: 5 mg of methylphenidate uptitrated to max of 20 mg of methylphenidate, if tolerated

Placebos: 1 placebo capsule increased to max of 2 capsules twice daily

Period Title: Period 1 (6 Weeks)
Started 35 34 35 37
Completed 32 33 32 36
Not Completed 3 1 3 1
Period Title: Washout (2 Weeks)
Started 32 33 32 36
Completed 32 31 32 35
Not Completed 0 2 0 1
Period Title: Period 2 (6 Weeks)
Started 32 31 32 35
Completed 32 31 32 34
Not Completed 0 0 0 1
Period Title: Washout (2 Weeks)
Started 32 31 32 34
Completed 31 29 31 32
Not Completed 1 2 1 2
Period Title: Period 3 (6 Weeks)
Started 31 29 31 32
Completed 31 29 29 32
Not Completed 0 0 2 0
Period Title: Washout (2 Weeks)
Started 31 29 29 32
Completed 31 28 27 32
Not Completed 0 1 2 0
Period Title: Period 4 (6 Weeks)
Started 31 28 27 32
Completed 31 27 26 31
Not Completed 0 1 1 1
Arm/Group Title Arm A Arm B Arm C Arm D Total
Hide Arm/Group Description

amantadine, placebo, modafinil, methylphenidate

Amantadine: 100 mg of amantadine increased to 200 mg of amantadine, if tolerated

Modafinil: 100 mg of modafinil increased to 200 mg of modafinil, if tolerated

Methylphenidate: 5 mg of methylphenidate uptitrated to max of 20 mg of methylphenidate, if tolerated

Placebos: 1 placebo capsule increased to max of 2 capsules twice daily

placebo, methylphenidate, amantadine, modafinil

Amantadine: 100 mg of amantadine increased to 200 mg of amantadine, if tolerated

Modafinil: 100 mg of modafinil increased to 200 mg of modafinil, if tolerated

Methylphenidate: 5 mg of methylphenidate uptitrated to max of 20 mg of methylphenidate, if tolerated

Placebos: 1 placebo capsule increased to max of 2 capsules twice daily

modafinil, amantadine, methylphenidate, placebo

Amantadine: 100 mg of amantadine increased to 200 mg of amantadine, if tolerated

Modafinil: 100 mg of modafinil increased to 200 mg of modafinil, if tolerated

Methylphenidate: 5 mg of methylphenidate uptitrated to max of 20 mg of methylphenidate, if tolerated

Placebos: 1 placebo capsule increased to max of 2 capsules twice daily

methylphenidate, modafinil, placebo and amantadine

Amantadine: 100 mg of amantadine increased to 200 mg of amantadine, if tolerated

Modafinil: 100 mg of modafinil increased to 200 mg of modafinil, if tolerated

Methylphenidate: 5 mg of methylphenidate uptitrated to max of 20 mg of methylphenidate, if tolerated

Placebos: 1 placebo capsule increased to max of 2 capsules twice daily

Total of all reporting groups
Overall Number of Baseline Participants 35 34 35 37 141
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 35 participants 34 participants 35 participants 37 participants 141 participants
48.3  (9.9) 46.9  (12.4) 46.1  (10.3) 45.8  (10.2) 46.8  (10.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants 34 participants 35 participants 37 participants 141 participants
Female
27
  77.1%
26
  76.5%
27
  77.1%
29
  78.4%
109
  77.3%
Male
8
  22.9%
8
  23.5%
8
  22.9%
8
  21.6%
32
  22.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 35 participants 34 participants 35 participants 37 participants 141 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
4
  11.4%
6
  17.6%
5
  14.3%
4
  10.8%
19
  13.5%
White
27
  77.1%
25
  73.5%
26
  74.3%
29
  78.4%
107
  75.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
4
  11.4%
3
   8.8%
4
  11.4%
4
  10.8%
15
  10.6%
1.Primary Outcome
Title Modified Fatigue Impact Scale (MFIS) Score
Hide Description 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.
Time Frame Week 5 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Amantadine Modafinil Methylphenidate
Hide Arm/Group Description:
1 placebo capsule increased to max of 2 capsules twice daily
100 mg of amantadine increased to 200 mg of amantadine, if tolerated.
100 mg of modafinil increased to 200 mg of modafinil, if tolerated.
5 mg of methylphenidate uptitrated to max of 20 mg of methylphenidate, if tolerated.
Overall Number of Participants Analyzed 123 124 124 127
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
40.6
(38.2 to 43.1)
41.3
(38.8 to 43.7)
39.0
(36.6 to 41.4)
38.6
(36.2 to 41.0)
2.Secondary Outcome
Title Quality of Life in Neurological Disorders (Neuro-QoL) Item Bank - Fatigue Score
Hide Description 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.
Time Frame Week 5 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Amantadine Modafinil Methylphenidate
Hide Arm/Group Description:
1 placebo capsule increased to max of 2 capsules twice daily.
100 mg of amantadine increased to 200 mg of amantadine, if tolerated.
100 mg of modafinil increased to 200 mg of modafinil, if tolerated.
5 mg of methylphenidate uptitrated to max of 20 mg of methylphenidate, if tolerated.
Overall Number of Participants Analyzed 123 124 124 127
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
53.1
(51.9 to 54.3)
53.0
(51.7 to 54.2)
52.5
(51.3 to 53.8)
52.0
(50.8 to 53.2)
3.Secondary Outcome
Title Epworth Sleepiness Scale (ESS) Score
Hide Description 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'.
Time Frame Week 5 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Amantadine Modafinil Methylphenidate
Hide Arm/Group Description:
1 placebo capsule increased to max of 2 capsules twice daily.
100 mg of amantadine increased to 200 mg of amantadine, if tolerated.
100 mg of modafinil increased to 200 mg of modafinil, if tolerated.
5 mg of methylphenidate uptitrated to max of 20 mg of methylphenidate, if tolerated.
Overall Number of Participants Analyzed 123 124 124 127
Least Squares Mean (95% Confidence Interval)
Unit of Measure: score on a scale
9.4
(8.7 to 10.1)
9.3
(8.6 to 10.1)
8.3
(7.6 to 9.1)
8.8
(8.1 to 9.6)
4.Post-Hoc Outcome
Title Acceptability of Treatment as Assessed by a Single Question Questionnaire
Hide Description Participants will answer yes or no to this question: "Taken into consideration the possible benefits and/or disadvantages of this medication, would you choose it, going forward to treat your MS fatigue?". The number of participants who answered "Yes" to this question is reported here.
Time Frame Week 5 of each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Amantadine Modafinil Methylphenidate
Hide Arm/Group Description:
1 placebo capsule increased to max of 2 capsules twice daily.
100 mg of amantadine increased to 200 mg of amantadine, if tolerated.
100 mg of modafinil increased to 200 mg of modafinil, if tolerated.
5 mg of methylphenidate uptitrated to max of 20 mg of methylphenidate, if tolerated.
Overall Number of Participants Analyzed 123 124 124 127
Measure Type: Count of Participants
Unit of Measure: Participants
39
  31.7%
41
  33.1%
55
  44.4%
55
  43.3%
Time Frame Adverse events were collected during each six-week medication period.
Adverse Event Reporting Description The numbers in the adverse event section are patients who constitute the safety dataset. These are patients who at least took one dose of that medication (whether or not they had their efficacy measured).
 
Arm/Group Title Placebo Amantadine Modafinil Methylphenidate
Hide Arm/Group Description 1 placebo capsule increased to max of 2 capsules twice daily. 100 mg of amantadine increased to 200 mg of amantadine, if tolerated. 100 mg of modafinil increased to 200 mg of modafinil, if tolerated. 5 mg of methylphenidate uptitrated to max of 20 mg of methylphenidate, if tolerated.
All-Cause Mortality
Placebo Amantadine Modafinil Methylphenidate
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/124 (0.00%)   0/127 (0.00%)   0/125 (0.00%)   0/129 (0.00%) 
Hide Serious Adverse Events
Placebo Amantadine Modafinil Methylphenidate
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/124 (0.00%)   2/127 (1.57%)   1/125 (0.80%)   0/129 (0.00%) 
Cardiac disorders         
Myocardiitis *  0/124 (0.00%)  1/127 (0.79%)  0/125 (0.00%)  0/129 (0.00%) 
Nervous system disorders         
MS exacerbation *  0/124 (0.00%)  0/127 (0.00%)  1/125 (0.80%)  0/129 (0.00%) 
Vascular disorders         
Pulmonary embolism *  0/124 (0.00%)  1/127 (0.79%)  0/125 (0.00%)  0/129 (0.00%) 
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo Amantadine Modafinil Methylphenidate
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   38/124 (30.65%)   49/127 (38.58%)   50/125 (40.00%)   51/129 (39.53%) 
Cardiac disorders         
Cardiac disorders *  3/124 (2.42%)  3/127 (2.36%)  2/125 (1.60%)  4/129 (3.10%) 
Ear and labyrinth disorders         
Ear and labyrinth disorders *  0/124 (0.00%)  1/127 (0.79%)  0/125 (0.00%)  0/129 (0.00%) 
Eye disorders         
Eye disorders *  0/124 (0.00%)  1/127 (0.79%)  2/125 (1.60%)  1/129 (0.78%) 
Gastrointestinal disorders         
Gastrointestinal disorders *  10/124 (8.06%)  14/127 (11.02%)  19/125 (15.20%)  13/129 (10.08%) 
General disorders         
General disorders *  2/124 (1.61%)  4/127 (3.15%)  5/125 (4.00%)  4/129 (3.10%) 
Immune system disorders         
Immune system disorders *  0/124 (0.00%)  1/127 (0.79%)  1/125 (0.80%)  0/129 (0.00%) 
Infections and infestations         
Infections and infestations *  3/124 (2.42%)  2/127 (1.57%)  2/125 (1.60%)  1/129 (0.78%) 
Injury, poisoning and procedural complications         
Injury, poisoning, and procedural complications *  1/124 (0.81%)  0/127 (0.00%)  0/125 (0.00%)  4/129 (3.10%) 
Metabolism and nutrition disorders         
Metabolism and nutrition disorders *  2/124 (1.61%)  1/127 (0.79%)  3/125 (2.40%)  0/129 (0.00%) 
Musculoskeletal and connective tissue disorders         
Musculoskeletal and connective tissue disorders *  4/124 (3.23%)  1/127 (0.79%)  2/125 (1.60%)  1/129 (0.78%) 
Nervous system disorders         
Nervous system disorders *  13/124 (10.48%)  24/127 (18.90%)  22/125 (17.60%)  20/129 (15.50%) 
Psychiatric disorders         
Psychiatric disorders *  10/124 (8.06%)  20/127 (15.75%)  18/125 (14.40%)  23/129 (17.83%) 
Renal and urinary disorders         
Renal and urinary disorders *  0/124 (0.00%)  0/127 (0.00%)  1/125 (0.80%)  0/129 (0.00%) 
Reproductive system and breast disorders         
Reproductive system *  1/124 (0.81%)  1/127 (0.79%)  2/125 (1.60%)  2/129 (1.55%) 
Respiratory, thoracic and mediastinal disorders         
Respiratory disorders *  0/124 (0.00%)  2/127 (1.57%)  2/125 (1.60%)  2/129 (1.55%) 
Skin and subcutaneous tissue disorders         
Skin and subcutaneous tissue disorders *  2/124 (1.61%)  2/127 (1.57%)  5/125 (4.00%)  0/129 (0.00%) 
Vascular disorders         
Vascular disorders *  1/124 (0.81%)  3/127 (2.36%)  3/125 (2.40%)  1/129 (0.78%) 
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Bardia Nourbakhsh
Organization: Johns Hopkins University
Phone: 4106141522
EMail: bnourba1@jhmi.edu
Layout table for additonal information
Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT03185065    
Other Study ID Numbers: IRB00119702
First Submitted: June 9, 2017
First Posted: June 14, 2017
Results First Submitted: September 24, 2020
Results First Posted: October 19, 2020
Last Update Posted: October 20, 2020