Project Summary

PCORI has identified multiple sclerosis (MS) as an important research topic. Patients, clinicians, and others want 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 a funding initiative in 2015 on Treatment of Multiple Sclerosis. This research project is one of the studies PCORI awarded as part this program.

This research project is in progress. PCORI will post the research findings on this page within 90 days after the results are final.

What is the research about?

Multiple sclerosis, or MS, is a health problem that causes the body’s immune system to attack the nerve cells in the brain and spinal cord, causing nerve damage. Fatigue is one of the most disabling symptoms people with MS have. There are few treatment options for fatigue, and doctors and patients have little information to guide the use of current treatments.

One way to treat fatigue in patients with MS is with medicine. Another option is cognitive behavioral therapy, or CBT. CBT helps people develop new behaviors and ways of thinking that can lessen the intensity and impact of fatigue.

In this study, the research team is comparing three ways of treating fatigue in patients with MS. The first is CBT. Modafinil, a medicine for fatigue, is the second way. The third way is a combination of these two therapies. The team is comparing how much each method lessens fatigue in MS patients. The team is also looking to see if certain patients respond better to one treatment over the others.

Who can this research help?

Results of this study may help patients with MS and their doctors decide whether to treat fatigue with CBT, modafinil, or both.

What is the research team doing?

The research team is recruiting patients in southeastern Michigan and Seattle, Washington, who have problems with fatigue from MS. The team is assigning patients to one of three treatment groups by chance: CBT by phone with a therapist, modafinil, or a combination of both. The CBT treatment includes eight weekly telephone calls to help patients manage fatigue, followed by two check-in calls from a therapist the following month. The CBT addresses issues such as setting goals, improving sleep, and conserving energy. On the follow-up calls, patients make plans for managing fatigue in the future.

At the start of the study, over the 12-week treatment period, and 12 weeks after treatment ends, the research team is asking patients about their fatigue, other MS symptoms, sleep, social functioning, and quality of life. Study participants wear a sensor around their wrists to track their physical activity.

Across the three treatment groups, the team is comparing patients’ levels of fatigue, how well they follow their treatment plan, and any side effects. The team is also comparing how well the treatments work for patients with MS who have other conditions, such as depression, sleep problems, a disability.

Patients with MS, their providers, payers, and national and regional MS organizations are helping to design the study and recruit participants.

Research methods at a glance

Design Elements Description
Design Randomized controlled trial
Population Adults ages 18 years and older with MS and chronic, problematic fatigue that interfered with daily activities for ≥3 months and an average Fatigue Severity Score (FSS) score of ≥4
  • Cognitive behavioral therapy
  • Modafinil
  • Cognitive behavioral therapy plus modafinil

Primary: fatigue impact

Secondary: fatigue impact

Timeframe Timeframe Length of follow-up for collecting data on primary outcomes. View Glossary 12-week follow-up for study outcome

Project Information

Tiffany Braley, MD, MS
Anna 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


Award Type
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
State State The state where the project originates, or where the primary institution or organization is located. View Glossary
Last updated: November 30, 2022