Prospective Case Series to Refine Standalone Cognitive Behavioral Therapy Components for Multiple Sclerosis Fatigue

This prospective case series will use mixed methods to examine the feasibility, acceptability, and initial effects of three telehealth cognitive behavioral therapy components (relaxation training, behavioral activation, cognitive therapy) for fatigue in people with multiple sclerosis.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Fatigue
• Intervention / Treatment: Behavioral: 4-week Relaxation Training; Behavioral: 4-week Behavioral Activation; Behavioral: 4-week Cognitive Therapy

Detailed Description

Fatigue affects 80% of people with multiple sclerosis (PwMS), and nearly half report fatigue as their most disabling symptom. The cognitive behavioral model of MS fatigue theorizes that MS disease factors trigger fatigue, but fatigue is maintained or worsened by factors like daily stress and how PwMS react cognitively, behaviorally, physiologically, and emotionally to fatigue. In-person and telehealth cognitive behavioral therapy (CBT) for fatigue targets these factors and reactions and is one of the most effective treatments for MS fatigue. However, CBT is resource intensive, as it consists of multiple components (i.e., relaxation training, behavioral activation, cognitive therapy), requiring 8-16 hour-long sessions delivered by a specialized clinician. CBT has yet to be assessed via an integrated translational model that considers all stages, from intervention development to implementation. Thus, the active components of CBT for MS fatigue and their mechanisms are unclear and, despite the significant burden of MS fatigue, CBT for fatigue is not widely accessible due to various implementation barriers.

The proposed prospective case series is the first of two project aims. The overall project aims to optimize CBT for fatigue to maximize efficacy and efficiency. It will use the Multiphase Optimization Strategy to advance scientific evidence on CBT's active components and facilitate implementation, thereby improving accessibility. The proposed prospective case series (Aim 1) will:

1. examine the feasibility and acceptability of telehealth CBT components (relaxation training, behavioral activation, cognitive therapy) for fatigue in PwMS.
2. examine initial effects of telehealth CBT components (relaxation training, behavioral activation, cognitive therapy) for improving fatigue in PwMS.
3. understand participants' perceptions of the feasibility, acceptability, appropriateness, and perceived effectiveness of telehealth CBT components (relaxation training, behavioral activation, cognitive therapy) for improving fatigue in PwMS and their recommendations for improving the CBT components.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98133
      • Multiple Sclerosis Center at UW Medical Center - Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. MS diagnosis of any subtype per chart review
2. Score 4 or higher on the Fatigue Severity Scale
3. Presence of chronic, problematic fatigue that, in the opinion of the patient, has interfered with their daily activities for 3 or more months
4. Are able to comply with study procedures and complete measures independently assessed via self-report
5. All genders
6. 18 years of age or older
7. Able to read and speak English
8. Are willing to maintain current fatigue treatment regimen for duration of study (although individuals who want to make a change to their fatigue treatment regimen will be considered eligible 3 months after making that change)

Exclusion Criteria:

1. Score greater than 7 on the Patient Determined Disease Steps Scale
2. Has significant cognitive impairment as indicated by 1 or more errors on the 6-item Cognitive Screener
3. Change in disease modifying medications in the prior three months assessed via self-report (although participants will be considered eligible after the 3-month window)
4. History of MS relapse within the last 30 days prior to screening assessed via self-report (although participants will be considered eligible after the 30-day window)
5. Current suicidal ideation with intent or plan as indicated by a score of 1 or higher on the Patient Health Questionnaire-9 suicide item and further assessment with the Columbia-Suicide Severity Rating Scale (although individuals with suicidal ideation but no intent or plan will be considered eligible)
6. Currently engaged in psychotherapy for fatigue assessed via self-report
7. Current pregnancy (although participants will be considered eligible when they are no longer pregnant)
8. Currently participating in another research study that could impact fatigue such as intervention studies targeting mood, energy management, exercise/physical activity, and diet (although participants can be screened for eligibility once they have completed the other research study).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Relaxation Training; Didactic and experiential training in one or more relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, autogenic relaxation, and guided imagery to reduce autonomic nervous system arousal.	Behavioral: 4-week Relaxation Training; A 4-session telehealth Relaxation Training intervention for multiple sclerosis fatigue that is derived from evidence-based multicomponent CBT for multiple sclerosis fatigue. The intervention is based on the cognitive behavioral model of fatigue in multiple sclerosis. The intervention involves 4, 30-60-minute sessions including the following content a) education about fatigue in multiple sclerosis and the cognitive behavioral model of multiple sclerosis fatigue, b) treatment rationale, b) didactic and experiential training in relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, autogenic relaxation, and guided imagery, and c) goal setting and problem-solving barriers focused on integrating relaxation practices into daily routine.
Experimental: Behavioral Activation; Didactic material and practice focused on identification and reduction of avoidance behaviors (e.g., excessive rest) and increased engagement in valued and reinforcing activities (e.g., physical activity, social engagement).	Behavioral: 4-week Behavioral Activation; A 4-session telehealth Behavioral Activation intervention for multiple sclerosis fatigue that is derived from evidence-based multicomponent CBT for multiple sclerosis fatigue. The intervention is based on the cognitive behavioral model of fatigue in multiple sclerosis. The intervention involves 4, 30-60-minute sessions including the following content a) education about fatigue in multiple sclerosis, the cognitive behavioral model of multiple sclerosis fatigue, and self-monitoring activity and energy, b) treatment rationale, c) identification of values/priorities to guide activities, d) activity planning, e) goal setting and problem-solving barriers to engaging in activities.
Experimental: Cognitive Therapy; Didactic material and practice focused on identifying, challenging, and modifying inaccurate and/or unhelpful patterns of thought about the self and the world (e.g., catastrophizing the meaning and consequences of fatigue) to change unwanted behavioral patterns (e.g., excessive rest).	Behavioral: 4-week Cognitive Therapy; A 4-session telehealth Cognitive Therapy intervention for multiple sclerosis fatigue that is derived from evidence-based multicomponent CBT for multiple sclerosis fatigue. The intervention is based on the cognitive behavioral model of fatigue in multiple sclerosis. The intervention involves 4, 30-60-minute sessions including the following content a) education about fatigue in multiple sclerosis, the cognitive behavioral model of multiple sclerosis fatigue, self-monitoring thoughts, and core beliefs, b) treatment rationale, b) labeling thoughts as helpful, unhelpful, or neutral, c) using distraction to cope with unhelpful thoughts, d) challenging and changing unhelpful thoughts, e) problem solving barriers to coping with or changing unhelpful thoughts.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intervention Acceptability	Intervention Acceptability will be measured with the Acceptability of Intervention Measure (AIM). When assessed via online survey, responses from the Intervention Acceptability items are averaged to create a mean score [1-5]. A higher score indicates more agreement with intervention acceptability while a lower score indicates less agreement with intervention acceptability.	Collected via online survey at post-treatment (approximately 4-8 weeks after the pre-treatment survey).
Intervention Appropriateness	Intervention Appropriateness will be measured with the Intervention Appropriateness Measure (IAM). When assessed via online survey, responses from the Intervention Appropriateness items are averaged to create a mean score [1-5]. A higher score indicates more agreement with intervention appropriateness while a lower score indicates less agreement with intervention appropriateness.	Collected via online survey at post-treatment (approximately 4-8 weeks after the pre-treatment survey).
Intervention Feasibility	Intervention Feasibility will be measured with the Feasibility of Intervention Measure (FIM). When assessed via online survey, responses from the Intervention Feasibility items are averaged to create a mean score [1-5]. A higher score indicates more agreement with intervention feasibility while a lower score indicates less agreement with intervention feasibility.	Collected via online survey at post-treatment (approximately 4-8 weeks after the pre-treatment survey).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatigue	Fatigue will be measured by the Modified Fatigue Impact Scale. This is a 21-item self-report questionnaire assessing fatigue-related symptoms in the previous four weeks via 5-point Likert-type scale. It yields a total score (range: 0-84) and a higher score indicates greater fatigue.	Collected via online survey at pre-treatment (up to 4 weeks before treatment session 1) and post-treatment (approximately 4-8 weeks after the pre-treatment survey).
Participation in Social Roles and Activities	Patient Reported Outcomes Measurement Information System Short Form - Ability to Participate in Social Roles and Activities (PROMIS-SRA; Hahn et al., 2010). The 8-item short form version of the PROMIS-SRA assesses the perceived ability to perform one's usual social roles and activities. Items are rated on a 5-point Likert-type scale. Raw summed scores are converted to T-scores standardized to the U.S. general population (mean = 50, standard deviation = 10), with higher scores indicating better ability to participate in social roles and activities.	Collected via online survey at pre-treatment (up to 4 weeks before treatment session 1) and post-treatment (approximately 4-8 weeks after the pre-treatment survey).
Relaxation/Serenity	Relaxation/Serenity will be measured by the Positive and Negative Affect Schedule Serenity Subscale. This is a 3-item self-report subscale of the Positive and Negative Affect Schedule assessing perceptions of feeling of calm, relaxed, and at ease over the previous week via a 5-point Likert-type scale. The summed total score ranges from 3-15 and a higher score indicates greater feelings of relaxation/serenity.	Collected via online survey at pre-treatment (up to 4 weeks before treatment session 1) and post-treatment (approximately 4-8 weeks after the pre-treatment survey).
Fatigue Catastrophizing	Fatigue catastrophizing will be measured by the Fatigue Catastrophizing Scale. This is a 13-item self-report questionnaire assessing negative beliefs or expectations connected to one's perceptions of fatigue via a 5-point Likert-type scale. Summed total scores range from 0 to 52, and a higher score indicates greater fatigue catastrophizing.	Collected via online survey at pre-treatment (up to 4 weeks before treatment session 1) and post-treatment (approximately 4-8 weeks after the pre-treatment survey).
Behavioral Activation	Behavioral activation will be measured by the Behavioral Activation for Depression Scale Short Form. This is a 9-item self-report measure. It assess the extent to which the respondent thinks they have engaged in pleasant and/or goal-directed activity over the past week via a 7-point Likert-type scale. Summed total scores range from 0 to 54, and a higher score indicates greater behavioral activation.	Collected via online survey at pre-treatment (up to 4 weeks before treatment session 1) and post-treatment (approximately 4-8 weeks after the pre-treatment survey).
Cognitive Behavioural Responses Questionnaire - Short Form	This is a 18-item self-report questionnaire consisting of five subscales assessing cognitive responses (fear avoidance beliefs, embarrassment avoidance beliefs, symptom focusing) and behavioral responses (resting or avoidance of activity, all-or-nothing behavior) to fatigue one's connected to one's perceptions of fatigue via a 5-point Likert-type scale. The summed total subscale scores range from 0 to 12, and higher scores indicate a more negative response to fatigue.	Collected via online survey at pre-treatment (up to 4 weeks before treatment session 1) and post-treatment (approximately 4-8 weeks after the pre-treatment survey).
Global Impression of Change	This is a single-item self-report scale that assess the perceived intervention-related change in one's activity limitations, symptoms, emotions, and overall quality of life via 7-point Likert-type scale. The score ranges from 0 to 6 and a higher score indicates greater perceived change.	Collected via online survey at post-treatment (approximately 4-8 weeks after the pre-treatment survey).

Collaborators and Investigators

• Sponsor: University of Washington
• Investigators: Principal Investigator: Lindsey Knowles, PhD, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2023
• Primary Completion (Actual): September 25, 2024
• Study Completion (Actual): September 25, 2024

Study Registration Dates

• First Submitted: April 27, 2023
• First Submitted That Met QC Criteria: April 27, 2023
• First Posted (Actual): May 8, 2023

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 13, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Cognitive behavioral therapy; Multiple sclerosis; Fatigue; Cognitive therapy; Relaxation training; Behavioral activation
• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Multiple Sclerosis; Fatigue; Therapeutics; Mind-Body Therapies; Complementary Therapies; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Cognitive Behavioral Therapy; Relaxation Therapy
• Other Study ID Numbers: STUDY00017623

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will make available to interested researchers a data file containing de-identified data used for each published article at the time the article is accepted for publication. The data will be de-identified to remove any variables from which it would be possible to identify any individual participants. Specifically, we will create a data file that includes all variables used in the published article and a list of the variables in the data file (along with variable labels) and send to investigators who request the data a copy of: (1) the published article (which will describe the source of the data); (2) the variable list/variable labels; and (3) the dataset (as an SPSS.sav file). Note, though, even though any data files that we share will be stripped of identifiers prior to release for sharing, it remains possible those who access the data could potentially use deduction to identify participants with unusual characteristics or combinations of unusual characteristics.
• IPD Sharing Time Frame: The data used for the analyses for any papers published will become available to interested researchers by request after that article is published. Those data will continue to be available for at least five years following the publication of the article.
• IPD Sharing Access Criteria: We will make the data and associated documentation available to users only under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying or returning the data after analyses are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No