Cognitive Behavioral Therapy, Modafinil, or Both for Multiple Sclerosis Fatigue
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis; Fatigue
Intervention: Telephone-based Cognitive Behavioral Therapy; Modafinil
Intervention description: Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.; Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).
Intervention MeSH terms: Modafinil
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking description: Rater blinded
Enrollment: 343.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: cognitive behavioral therapy; modafinil; Provigil; fatigue; MS

Summary:

      This clinical trial will compare the effectiveness of 3 treatments for fatigue in Multiple
      Sclerosis: 1) a commonly used behavioral treatment strategy (telephone-based cognitive
      behavioral therapy), 2) a commonly used medication (modafinil), and 3) a combination of both
      therapies. Each participant will receive one of these 3 treatments for a total of 12 weeks.
      Hypotheses are that, at 12 weeks, treatment with combination therapy will overall lead to
      greater reductions in fatigue impact, fatigue severity, and fatigability compared to
      monotherapy, and that comorbid depression, sleep disturbances, and baseline disability level
      will be important effect modifiers that influence treatment effect and adherence.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with clinically definite Multiple Sclerosis (MS, all MS subtypes);

          2. Age 18 years or older;

          3. Presence of chronic, problematic fatigue that, in the opinion of the patient, has
             interfered with their daily activities for ≥ 3 months;

          4. Average Fatigue Severity Scale (FSS) score greater or equal to 4 at screening.

        Exclusion Criteria:

          1. Current shift work sleep disorder, or narcolepsy diagnosed with polysomnography and
             multiple sleep latency test

          2. History of MS relapse within the last 30 days prior to screening (participants will be
             considered eligible after the 30-day window);

          3. Current stimulant or wake-promoting agent use (such as amantadine, modafinil,
             methylphenidate, or amphetamine) within 30 days of screening;

          4. Pregnancy or breastfeeding;

          5. Reliance on hormonal contraception AND concomitant unwillingness to use alternative
             non-hormonal means of birth control (spermicide or condoms) during the course of the
             study;

          6. Current suicidal ideation (SI) with intent or plan;

          7. Known hypersensitivity to modafinil or armodafinil or its inactive ingredients;

          8. History of the following cardiovascular conditions: recent myocardial infarction (last
             6 months prior to screening), unstable angina, left ventricular hypertrophy, mitral
             valve prolapse, NYHA class III or IV congestive heart failure;

          9. History of prescription or illicit stimulant abuse (such as cocaine, amphetamine,
             methamphetamine);

         10. Any other medical, neurological, or psychiatric condition that, in the opinion of the
             investigators, could affect participant safety or eligibility.