Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE June 9, 2017
First Posted Date  ICMJE June 14, 2017
Results First Submitted Date  ICMJE September 24, 2020
Results First Posted Date  ICMJE October 19, 2020
Last Update Posted Date October 20, 2020
Actual Study Start Date  ICMJE October 4, 2017
Actual Primary Completion Date November 21, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 24, 2020)
Modified Fatigue Impact Scale (MFIS) Score [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 9, 2017)
Modified Fatigue Impact Scale (MFIS) Score [ Time Frame: Week 5 of each treatment period ]
MFIS score at the end o each treatment period
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2020)
  • Quality of Life in Neurological Disorders (Neuro-QoL) Item Bank - Fatigue Score [ Time Frame: 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.
  • Epworth Sleepiness Scale (ESS) Score [ Time Frame: 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'.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 9, 2017)
  • Neuro-QoL Item Bank - Fatigue score [ Time Frame: Week 5 of each treatment period ]
    Neuro-QoL Item Bank - Fatigue score at the end o each treatment period
  • Epworth Sleepiness Scale (ESS) Score [ Time Frame: Week 5 of each treatment period ]
    ESS score at the end o each treatment period
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treatment of Fatigue With Methylphenidate, Modafinil and Amantadine in Multiple Sclerosis
Official Title  ICMJE Treatment of Fatigue With Methylphenidate, Modafinil and Amantadine in Multiple Sclerosis
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
randomized, placebo-controlled, crossover, 4-sequence, 4-period, double-blind, multicenter trial of 3 commonly used medications for treatment of Multiple Sclerosis related fatigue versus placebo in fatigued subjects with MS.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double-blind
Primary Purpose: Treatment
Condition  ICMJE Fatigue in Multiple Sclerosis
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: Arm A
    amantadine, placebo, modafinil, methylphenidate
    Interventions:
    • Drug: Amantadine
    • Drug: Modafinil
    • Drug: Methylphenidate
    • Drug: Placebos
  • Experimental: Arm B
    placebo, methylphenidate, amantadine, modafinil
    Interventions:
    • Drug: Amantadine
    • Drug: Modafinil
    • Drug: Methylphenidate
    • Drug: Placebos
  • Experimental: Arm C
    modafinil, amantadine, methylphenidate, placebo
    Interventions:
    • Drug: Amantadine
    • Drug: Modafinil
    • Drug: Methylphenidate
    • Drug: Placebos
  • Experimental: Arm D
    methylphenidate, modafinil, placebo and amantadine
    Interventions:
    • Drug: Amantadine
    • Drug: Modafinil
    • Drug: Methylphenidate
    • Drug: Placebos
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 24, 2020)
141
Original Estimated Enrollment  ICMJE
 (submitted: June 9, 2017)
136
Actual Study Completion Date  ICMJE November 21, 2019
Actual Primary Completion Date November 21, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  • Age 18 years and older.
  • Females of childbearing age must have a negative urine pregnancy test at baseline and use an effective method of contraception during the study.
  • Diagnosis of MS (according to the 2010 McDonald criteria).
  • Expanded Disability Status Scale (EDSS) score at the time of screening 0.0-7.0.
  • Fatigue reportedly present and screening Modified Fatigue Impact Scale (MFIS) score more than 33.
  • At least a two-week washout for any fatigue-related drug, including study medications.

Exclusion criteria:

  • Neurodegenerative disorders other than relapsing or progressive MS.
  • Breastfeeding or pregnant.
  • History of coronary artery disease or congestive heart failure.
  • Uncontrolled hypertension at screening (history of high blood pressure and screening systolic blood pressure >160 or diastolic blood pressure>100).
  • Glomerular Filtration Rate (GFR) (glomerular filtration rate) < 50.
  • Abnormal liver function at screening (AST or Alanine Aminotransferase (ALT) more than twice the upper limit of normal).
  • Terminal medical conditions.
  • Currently treated for active malignancy.
  • Planned surgery or move within 8 months of screening.
  • Alcohol or substance abuse in the past year (except marijuana or other cannabinoids).
  • A history of intolerance or allergic or anaphylactic reaction to amantadine, modafinil, methylphenidate or any component of the preparation.
  • Clinically unstable medical or psychiatric disorders that require acute treatment as determined by the PI.
  • Concurrent use of monoamine oxidase inhibitors-B.
  • Hypersensitivity/idiosyncrasy to sympathomimetic amines
  • Inability to communicate or answer the questionnaires in English or Spanish.
  • Severe untreated anemia (blood hemoglobin <9gr/dl)
  • History of untreated hypothyroidism
  • History of untreated sleep apnea
  • History of long QT syndrome, atrial fibrillation or tachyarrhythmias (other than sinus tachycardia)
  • History of ischemic or hemorrhagic stroke
  • History of glaucoma
  • History of Tourette syndrome
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03185065
Other Study ID Numbers  ICMJE IRB00119702
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Johns Hopkins University
Study Sponsor  ICMJE Johns Hopkins University
Collaborators  ICMJE Patient-Centered Outcomes Research Institute
Investigators  ICMJE
Principal Investigator: Bardia Nourbakhsh, MD Johns Hopkins University
PRS Account Johns Hopkins University
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP