Cognitive Behavioral Therapy, Modafinil, or Both for Multiple Sclerosis Fatigue (COMBO-MS)

University of Michigan

Status and phase: Completed; Phase 4

Conditions: Multiple Sclerosis

Treatments: Behavioral: Telephone-based Cognitive Behavioral Therapy; Drug: Modafinil

Study type: Interventional

Funder types: Other

Identifiers

NCT03621761

HUM00143319

Details and patient eligibility

About

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.

Enrollment: 343 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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343 participants in 3 patient groups

Cognitive Behavioral Therapy

Active Comparator group

Description:

8 weekly telephone-based sessions and 2 booster sessions

Treatment:

Behavioral: Telephone-based Cognitive Behavioral Therapy

Modafinil

Active Comparator group

Description:

50-400 mg per day (oral)

Treatment:

Drug: Modafinil

Cognitive Behavioral Therapy + Modafinil

Active Comparator group

Description:

Telephone-based cognitive behavioral therapy (8 weekly therapy sessions and 2 booster sessions) + Modafinil 50-400 mg per day (oral)

Treatment:

Drug: Modafinil

Behavioral: Telephone-based Cognitive Behavioral Therapy