Results Summary

What was the research about?

Multiple sclerosis, or MS, is a condition that affects the central nervous system. Fatigue is a common and disabling symptom of MS.

In this study, the research team wanted to learn how well three treatments helped people with MS feel less fatigued:

  • Cognitive behavioral therapy, or CBT. In CBT, patients learn how to change patterns in their thinking and behavior.
  • Modafinil, a medicine for fatigue.
  • Both CBT and modafinil.

The research team also looked at how much people reported that their MS symptoms and quality of life improved since starting treatment.

What were the results?

After three months, with all three treatments, people felt less fatigued. The level of improvement was about the same for all three treatments.

Compared with modafinil alone, people who received both treatments reported more overall benefits since starting treatment. Compared with CBT alone, people who received modafinil alone or both treatments didn’t differ in their sense of overall improvement.

More people who received modafinil alone or with CBT had side effects than people who received CBT alone. The most common side effects for modafinil were headache, insomnia, and anxiety. Few people stopped treatment.

Who was in the study?

The study included 336 adults with MS and fatigue. Of these, 85 percent were White, 6 percent were Black, 1 percent were Asian, 6 percent were more than one race, and 1 percent were another race. The average age was 49, and 76 percent were women. The study took place at two MS centers in Michigan and Washington.

What did the research team do?

The research team assigned people by chance to one of the three treatments. With CBT, people had eight sessions where they learned skills to lessen the impact of fatigue. They also had two optional sessions where they learned how to keep using those skills. People completed sessions by phone for three months. People took modafinil by mouth twice a day as needed for three months. People who received CBT and modafinil received both treatments together for three months.

At the start of the study and again three months later, people completed an online survey about fatigue, symptoms, function, and quality of life. They also wore a device on the wrist, called PRO-Diary, for one week at the start of the study and three months later. The device measured how active they were and their sleep patterns. The research team gave people instructions on how to use PRO-Diary at home.

People with MS, doctors, MS center staff, a health insurer, and advocacy groups helped plan the study.

What were the limits of the study?

The study took place at two MS centers, and most people in the study were White. Results may differ in other places or for patients from other racial backgrounds.

Future research could look at other health outcomes that matter to patients with MS.

How can people use the results?

People with MS and their doctors can use the results when considering ways to treat fatigue.

PCORI identified multiple sclerosis (MS) as an important research topic. People with MS, clinicians, and others wanted to learn how different treatment strategies, aimed at changing specific symptoms or the overall course of MS, affect patients’ symptoms and quality of life. To address this issue, PCORI launched an initiative in 2015 on Treatment of Multiple Sclerosis. The initiative funded this research project and others.

Final Research Report

This project's final research report is expected to be available by May 2024.

Peer-Review Summary

Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study. 

The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments.   

Peer reviewers commented and the researchers made changes or provided responses. Those comments and responses included the following: 

  • The reviewers asked the researchers to state more clearly that there were no clinically or statistically significant differences between the treatment arms in this study. The researchers revised their language in the abstract and in the discussion to clarify this lack of between-group difference and to add caveats to their assertions that all three treatment arms improved patient-reported fatigue. 

  • The reviewers felt that the associations between patient characteristics and treatment effects described in the report varied considerably for the primary and secondary outcomes, so they raised the question about whether such differences were sufficiently robust to guide treatment. In addition, these analyses have a high potential for false positives due to multiple statistical tests. The researchers explained that they did not adjust their analyses for multiple comparisons because they understood such adjustments to be a controversial issue. The reviewers insisted that the researchers should at least remind the readers that there was the possibility of increased false positives because they did not adjust for multiple comparisons. 

  • The reviewers noted that a limitation of this study was the lack of sensitivity analyses to assess whether missing data significantly affected the analytic results. The researchers explained that their rates of missing data on the primary outcome were low but they presented the results of analyses after imputation. They also clarified that they conducted complete-case analyses for their secondary outcomes.

Conflict of Interest Disclosures

Project Information

Tiffany J. Braley, MD, MS
Anna L. Kratz, PhD
University of Michigan
$3,359,830
A Randomized Controlled Trial of Telephone-Delivered Cognitive Behavioral Therapy, Modafinil, and Combination Therapy of Both Interventions for Fatigue in Multiple Sclerosis

Key Dates

September 2017
April 2023
2017
2023

Study Registration Information

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Health Conditions Health Conditions These are the broad terms we use to categorize our funded research studies; specific diseases or conditions are included within the appropriate larger category. Note: not all of our funded projects focus on a single disease or condition; some touch on multiple diseases or conditions, research methods, or broader health system interventions. Such projects won’t be listed by a primary disease/condition and so won’t appear if you use this filter tool to find them. View Glossary
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Intervention Strategy Intervention Strategies PCORI funds comparative clinical effectiveness research (CER) studies that compare two or more options or approaches to health care, or that compare different ways of delivering or receiving care. View Glossary
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Last updated: March 14, 2024