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

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ClinicalTrials.gov Identifier: NCT03621761
Recruitment Status : Completed
First Posted : August 8, 2018
Results First Posted : December 27, 2022
Last Update Posted : December 27, 2022
Sponsor:
Collaborators:
University of Washington
Patient-Centered Outcomes Research Institute
National Multiple Sclerosis Society
Information provided by (Responsible Party):
Tiffany J. Braley, MD, MS, University of Michigan

Study Description
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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.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Behavioral: Telephone-based Cognitive Behavioral Therapy Drug: Modafinil Phase 4

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 343 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description: Rater blinded
Primary Purpose: Treatment
Official Title: A Randomized Controlled Trial of Telephone-delivered Cognitive Behavioral-therapy, Modafinil, and Combination Therapy of Both Interventions for Fatigue in Multiple Sclerosis
Actual Study Start Date : November 15, 2018
Actual Primary Completion Date : August 24, 2021
Actual Study Completion Date : November 30, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Modafinil

Arms and Interventions
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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 Name: 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 Name: Provigil


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03621761


Locations
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United States, Michigan
The University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Washington
The University of Washington
Seattle, Washington, United States, 98195
Sponsors and Collaborators
University of Michigan
University of Washington
Patient-Centered Outcomes Research Institute
National Multiple Sclerosis Society
Investigators
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Principal Investigator: Tiffany J Braley, MD, MS University of Michigan
  Study Documents (Full-Text)

Documents provided by Tiffany J. Braley, MD, MS, University of Michigan:
Study Protocol and Statistical Analysis Plan  [PDF] May 7, 2020

More Information
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Publications:

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Responsible Party: Tiffany J. Braley, MD, MS, Assistant Professor of Neurology, University of Michigan
ClinicalTrials.gov Identifier: NCT03621761    
Other Study ID Numbers: HUM00143319
First Posted: August 8, 2018    Key Record Dates
Results First Posted: December 27, 2022
Last Update Posted: December 27, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Tiffany J. Braley, MD, MS, University of Michigan:
cognitive behavioral therapy
modafinil
Provigil
fatigue
MS
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Fatigue
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
 Immune System Diseases
Modafinil
Central Nervous System Stimulants
Physiological Effects of Drugs
Wakefulness-Promoting Agents
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action