Clinical trial NCT03621761: Cognitive Behavioral Therapy, Modafinil, or Both for Multiple Sclerosis Fatigue
Official title: A Randomized Controlled Trial of Telephone-delivered Cognitive Behavioral-therapy, Modafinil, and Combination Therapy of Both Interventions for Fatigue in Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Sclerosis
Keywords: cognitive behavioral therapy
modafinil
Provigil
fatigue
MS
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: University of Washington
name: Patient-Centered Outcomes Research Institute
name: National Multiple Sclerosis Society
First posted: 2018-08-08
Enrollment: 343
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change in the Modified Fatigue Impact Scale (MFIS) Score
timeFrame: Baseline-12 weeks
Secondary outcomes:
measure: Change in Fatigue Intensity as Assessed by Self-reported Numerical Rating Scale (NRS) Score.
timeFrame: Baseline-12 weeks
measure: Change in Fatigue Interference as Assessed by Self-reported Numerical Rating Scale (NRS) Score
timeFrame: Baseline-12 weeks
measure: Change in Fatigability as Assessed by the Self-reported Fatigue Intensity Numerical Rating Scale (NRS) Score and Physical Activity Level
timeFrame: Baseline-12 weeks
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: The University of Michigan
state: Michigan
city: Seattle
country: United States
facility: The University of Washington
state: Washington
Study officials:
affiliation: University of Michigan
name: Tiffany J Braley, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989 Oct;46(10):1121-3. doi: 10.1001/archneur.1989.00520460115022.
citation: Kroenke K, Spitzer RL, Williams JB. The Patient Health Questionnaire-2: validity of a two-item depression screener. Med Care. 2003 Nov;41(11):1284-92. doi: 10.1097/01.MLR.0000093487.78664.3C.
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