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

NCT03185065 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: IRB00119702
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 2

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.

Conditions

Fatigue in Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Modified Fatigue Impact Scale (MFIS) Score

  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.

  Week 5 of each treatment period

Secondary Outcomes (2)

• Quality of Life in Neurological Disorders (Neuro-QoL) Item Bank - Fatigue Score

  Week 5 of each treatment period

• Epworth Sleepiness Scale (ESS) Score

  Week 5 of each treatment period

Study Arms (4)

Arm A

EXPERIMENTAL

amantadine, placebo, modafinil, methylphenidate

Drug: Amantadine; Drug: Modafinil; Drug: Methylphenidate; Drug: Placebos

Arm B

EXPERIMENTAL

placebo, methylphenidate, amantadine, modafinil

Drug: Amantadine; Drug: Modafinil; Drug: Methylphenidate; Drug: Placebos

Arm C

EXPERIMENTAL

modafinil, amantadine, methylphenidate, placebo

Drug: Amantadine; Drug: Modafinil; Drug: Methylphenidate; Drug: Placebos

Arm D

EXPERIMENTAL

methylphenidate, modafinil, placebo and amantadine

Drug: Amantadine; Drug: Modafinil; Drug: Methylphenidate; Drug: Placebos

Interventions

Amantadine DRUG

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

Arm A; Arm B; Arm C; Arm D

Modafinil DRUG

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

Arm A; Arm B; Arm C; Arm D

Methylphenidate DRUG

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

Arm A; Arm B; Arm C; Arm D

Placebos DRUG

1 placebo capsule increased to max of 2 capsules twice daily

Arm A; Arm B; Arm C; Arm D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead
• Patient-Centered Outcomes Research Institute: collaborator

Study Sites (2)

University of California San Francisco

San Francisco, California, 94158, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Related Publications (2)

• Nourbakhsh B, Revirajan N, Morris B, Cordano C, Creasman J, Manguinao M, Krysko K, Rutatangwa A, Auvray C, Aljarallah S, Jin C, Mowry E, McCulloch C, Waubant E. Safety and efficacy of amantadine, modafinil, and methylphenidate for fatigue in multiple sclerosis: a randomised, placebo-controlled, crossover, double-blind trial. Lancet Neurol. 2021 Jan;20(1):38-48. doi: 10.1016/S1474-4422(20)30354-9. Epub 2020 Nov 23.

  PMID: 33242419 DERIVED

• Nourbakhsh B, Revirajan N, Waubant E. 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.

  PMID: 29113955 DERIVED

MeSH Terms

Interventions

Amantadine; Modafinil; Methylphenidate

Intervention Hierarchy (Ancestors)

Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Bardia Nourbakhsh
• Organization: Johns Hopkins University

bnourba1@jhmi.edu

4106141522

Study Officials

• Bardia Nourbakhsh, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 9, 2017
• First Posted: June 14, 2017
• Study Start: October 4, 2017
• Primary Completion: November 21, 2019
• Study Completion: November 21, 2019
• Last Updated: October 20, 2020
• Results First Posted: October 19, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)