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

December 5, 2022 updated by: Tiffany J. Braley, MD, MS, University of Michigan

A Randomized Controlled Trial of Telephone-delivered Cognitive Behavioral-therapy, Modafinil, and Combination Therapy of Both Interventions for Fatigue in Multiple Sclerosis

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

343

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • The University of Michigan
    • Washington
      • Seattle, Washington, United States, 98195
        • The University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Cognitive Behavioral Therapy
8 weekly telephone-based sessions and 2 booster sessions
Behavioral: Telephone-based Cognitive Behavioral Therapy
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.
Active Comparator: Modafinil
50-400 mg per day (oral)
Drug: Modafinil
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).
Other Names:
  • Provigil
Active Comparator: Cognitive Behavioral Therapy + Modafinil
Telephone-based cognitive behavioral therapy (8 weekly therapy sessions and 2 booster sessions) + Modafinil 50-400 mg per day (oral)
Behavioral: Telephone-based Cognitive Behavioral Therapy
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.
Drug: Modafinil
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).
Other Names:
  • Provigil

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the Modified Fatigue Impact Scale (MFIS) Score
Time Frame: Baseline-12 weeks
The Modified Fatigue Impact Scale is a 21-item self-report survey. Each item is rated 0-4, Total scores range from 0-84. . Higher scores indicate a greater impact of fatigue on a person's activities. The primary outcome measure will be the mean within-subject difference between baseline and 12-week Modified Fatigue Impact Scale values (delta-MFIS), compared between the 3 treatment groups.
Baseline-12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Fatigue Intensity as Assessed by Self-reported Numerical Rating Scale (NRS) Score.
Time Frame: Baseline-12 weeks
Fatigue intensity was assessed using a wearable monitor, the PRO-Diary (CamNtech) - a wrist-worn accelerometer-based activity monitor which also contains a self-report user interface. Using a 0-10 numerical rating scale, participants entered fatigue intensity ratings into the user-interface on the PRO-Diary 4 times each day, for 7 days, at baseline (pre-intervention) and at 12 weeks post-intervention. All scores over the 7 days were averaged to produce an aggregate fatigue intensity score. Higher scores indicate greater fatigue intensity. Change in fatigue intensity between baseline and 12 weeks was compared between the 3 treatment groups.
Baseline-12 weeks
Change in Fatigue Interference as Assessed by Self-reported Numerical Rating Scale (NRS) Score
Time Frame: Baseline-12 weeks
Fatigue interference will be assessed using a wearable monitor, the PRO-Diary (CamNtech) - a wrist-worn accelerometer-based activity monitor which also contains a self-report user interface. Using a 0-10 numerical rating scale, participants entered fatigue interference ratings into the user-interface on the PRO-Diary 4 times each day, for 7 days, at baseline (pre-intervention) and at 12 weeks post-intervention. All scores over the 7 days were averaged to produce an aggregate fatigue impact score. Higher scores indicate greater fatigue impact. Change in fatigue interference between baseline and 12 weeks will be compared between the 3 treatment groups.
Baseline-12 weeks
Change in Fatigability as Assessed by the Self-reported Fatigue Intensity Numerical Rating Scale (NRS) Score and Physical Activity Level
Time Frame: Baseline-12 weeks
Fatigability will be assessed using a wearable monitor, the PRO-Diary (CamNtech) - a wrist-worn accelerometer-based activity monitor which also contains a self-report user interface. The fatigability score will be calculated as the ratio of the self-reported fatigue intensity rating (using a 0-10 numerical rating score) divided by the participant's concurrent physical activity level (measured as the average number of activity counts per minute via actigraphy). All fatigability scores will be averaged over the 7 days to create an aggregate fatigability score. Higher scores indicate greater fatigability. Change in fatigability between baseline and 12 weeks will be compared between the 3 treatment groups.
Baseline-12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Michigan

Collaborators

Patient-Centered Outcomes Research Institute
University of Washington
National Multiple Sclerosis Society

Investigators

  • Principal Investigator: Tiffany J Braley, MD, MS, University of Michigan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 15, 2018

Primary Completion (Actual)

August 24, 2021

Study Completion (Actual)

November 30, 2021

Study Registration Dates

First Submitted

August 3, 2018

First Submitted That Met QC Criteria

August 3, 2018

First Posted (Actual)

August 8, 2018

Study Record Updates

Last Update Posted (Actual)

December 27, 2022

Last Update Submitted That Met QC Criteria

December 5, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HUM00143319

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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