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Phase 3 N=141 Randomized Quadruple-blind Treatment

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

Fatigue in Multiple Sclerosis

Enrolled (actual)
141
Serious AEs
0.6%
Results posted
Oct 2020
Primary outcome: Primary: Modified Fatigue Impact Scale (MFIS) Score — 40.6; 41.3; 39.0; 38.6 score on a scale

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Amantadine (Drug); Modafinil (Drug); Methylphenidate (Drug); Placebos (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Johns Hopkins University
Primary completion
Nov 2019

Outcome Measures

OutcomeResultp-value
PRIMARY
Modified Fatigue Impact Scale (MFIS) Score
40.6; 41.3; 39.0; 38.6
SECONDARY
Quality of Life in Neurological Disorders (Neuro-QoL) Item Bank - Fatigue Score
53.1; 53.0; 52.5; 52.0
SECONDARY
Epworth Sleepiness Scale (ESS) Score
9.4; 9.3; 8.3; 8.8

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.

Eligibility Criteria

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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03185065). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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