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

The Peer-Review Summary for this study will be posted here soon.

Project Information

Tiffany J. Braley, MD, MS
Anna L. Kratz, PhD
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

Key Dates

September 2017
April 2023

Study Registration Information


Has Results
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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
Populations Populations PCORI is interested in research that seeks to better understand how different clinical and health system options work for different people. These populations are frequently studied in our portfolio or identified as being of interest by our stakeholders. View Glossary
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: October 19, 2023