Treatment of Fatigue With Methylphenidate, Modafinil and Amantadine in Multiple Sclerosis
Condition: Fatigue in Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis; Fatigue
Intervention: Amantadine; Modafinil; Methylphenidate; Placebos
Intervention description: 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; 1 placebo capsule increased to max of 2 capsules twice daily
Intervention MeSH terms: Amantadine; Methylphenidate; Modafinil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
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
Enrollment: 141.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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