Factorial Optimization Trial to Test Cognitive Behavioral Therapy Components for Multiple Sclerosis Fatigue

Not Applicable

Recruiting

• Conditions: Multiple Sclerosis

• Registration Number: NCT06809192
• Lead Sponsor: University of Washington

Brief Summary

This randomized controlled factorial trial will examine whether and how relaxation training, behavioral activation, and cognitive therapy improve fatigue and functioning in fatigued adults living with multiple sclerosis.

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.

This optimization randomized controlled trial is the second aim of a research project using the Multiphase Optimization Strategy to optimize CBT for MS fatigue (1K23HD111628, Knowles, PI). This trial employs a balanced factorial design to test the main and interactive effects of the three telehealth CBT components: Relaxation Training, Behavioral Activation, and Cognitive Therapy. In this trial, each CBT component corresponds to an experimental factor that is being manipulated to obtain information about the CBT component. Each factor has two levels (Included or Excluded). The investigators are testing three factors/CBT components, yielding a 2\^3 factorial trial with eight experimental conditions. Each condition corresponds to a combination of levels of the 3 factors/CBT components (e.g., a participant may be randomly assigned to a condition including zero, one, two, or three CBT components). Participants will be offered the choice of completing treatment by telephone or videoconference. Participants will complete patient reported outcome measures at pre-intervention, post-intervention, and 3 months post-intervention (follow-up). A random sample of two participants from each trial condition with at least one component will also complete qualitative interviews at post-intervention.

The overall project aims to optimize CBT for fatigue to maximize efficacy and efficiency. The project uses the Multiphase Optimization Strategy to advance scientific evidence on CBT's active components and facilitate implementation, thereby improving accessibility.

Study Timeline

• Status Verified: 2025-01
• Study Start: 2025-01-10
• Study First Submitted: 2025-01-22
• Study First Submitted QC: 2025-01-29
• Last Update Submitted: 2025-03-24
• Study First Posted: 2025-03-25
• Last Update Posted: 2025-03-30
• Primary Completion: 2027-07-31
• Study Completion: 2027-07-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 112

Inclusion Criteria

1. Confirmed MS diagnosis of any subtype
2. Score of 4 or higher on the Fatigue Severity Scale
3. Able to fluently converse and read in English
4. 18 years of age or older
5. Able to comply with study procedures and complete self-report measures
6. Willing to have intervention sessions audiotaped for fidelity coding
7. Has experienced fatigue for 3 or more months

Exclusion Criteria

1. MS relapse within last 30 days (although participants will be considered eligible after the 30-day window)
2. Change in disease modifying medications (DMTs) in the prior three months (although participants will be considered eligible after the 3-month window)
3. Current suicidal ideation with intent or plan as indicated by a score of ≥1 on the Patient Health Questionnaire-9 suicide item and further assessment via the Columbia Suicide Severity Rating Scale (although individuals with suicidal ideation but no intent or plan will be considered eligible)
4. Currently engaged in psychotherapy for fatigue
5. 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 again once they have completed the other research study)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Primary Outcome Measures

Name	Time	Method
Modified Fatigue Impact Scale	Collected via online survey at baseline/pre-treatment, post-treatment (3 days after last treatment session or 2 months post-randomization for participants in the No Treatment condition), and 3-month follow-up.	This is a 21-item self-report questionnaire assessing fatigue-related symptoms in the previous four weeks via 5-point Likert-type scale. A higher score indicates greater fatigue.
PROMIS Short Form - Ability to Participate in Social Roles and Activities	Collected via online survey at baseline/pre-treatment, post-treatment (3 days after last treatment session or 2 months post-randomization for participants in the No Treatment condition), and 3-month follow-up.	This 8-item short form is a self-report questionnaire that assesses the perceived ability to perform one's usual social roles and activities via 5-point Likert-type scale. A lower score indicates lower ability to participate in social roles and activities.

Secondary Outcome Measures

Name	Time	Method
Perceived Stress Questionnaire - Tension scale	Collected via online survey at baseline/pre-treatment, post-treatment (3 days after last treatment session or 2 months post-randomization for participants in the No Treatment condition), and 3-month follow-up.	This is a 5-item self-report scale assessing tense disquietude, exhaustion, and the lack of relaxation via a 4-point Likert-type scale. A higher score indicates greater tension.
PROMIS Sleep Disturbance Short Form 4a	Collected via online survey at baseline/pre-treatment, post-treatment (3 days after last treatment session or 2 months post-randomization for participants in the No Treatment condition), and 3-month follow-up.	This is a 4-item self-report questionnaire assessing sleep disturbance via a 5-point Likert-type scale.
Behavioral Activation for Depression Scale Short Form	Collected via online survey at baseline/pre-treatment, post-treatment (3 days after last treatment session or 2 months post-randomization for participants in the No Treatment condition), and 3-month follow-up.	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. A higher score indicates greater behavioral activation.
Fatigue Catastrophizing Scale	Collected via online survey at baseline/pre-treatment, post-treatment (3 days after last treatment session or 2 months post-randomization for participants in the No Treatment condition), and 3-month follow-up.	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. A higher score indicates greater fatigue catastrophizing.
The Multiple Sclerosis-Fatigue Self Efficacy Scale	Collected via online survey at baseline/pre-treatment, post-treatment (3 days after last treatment session or 2 months post-randomization for participants in the No Treatment condition), and 3-month follow-up.	This is a 8-item self-report measure. It assesses the extent to which the respondent believes that they can manage and/or control their fatigue via a 10-point Likert-type scale. A higher score indicates greater fatigue self-efficacy.
Perceived Stress Scale	Collected via online survey at baseline/pre-treatment, post-treatment (3 days after last treatment session or 2 months post-randomization for participants in the No Treatment condition), and 3-month follow-up.	This is a 10-item self-report measure. It assess the extent to which the respondent perceives their life as unpredictable, uncontrollable, and overloaded via a 5-point Likert-type scale. A higher score indicates greater perceived stress.
Positive and Negative Affect Schedule	Collected via online survey at baseline/pre-treatment, post-treatment (3 days after last treatment session or 2 months post-randomization for participants in the No Treatment condition), and 3-month follow-up.	This is a 20-item self-report scale assessing the extent to which the respondent experiences positive and negative emotional states via a 5-point Likert-type scale. Higher Positive Affect scores indicate more positive affect, while higher Negative Affect scores indicate more negative affect.
PROMIS Emotional Distress-Depression - Short Form 4a	Collected via online survey at baseline/pre-treatment, post-treatment (3 days after last treatment session or 2 months post-randomization for participants in the No Treatment condition), and 3-month follow-up.	This 4-item short form is a self-report questionnaire that assesses depression symptoms via 5-point Likert-type scale. A higher score indicates greater depression.
EQ-5D-5L	Collected via online survey at baseline/pre-treatment, post-treatment (3 days after last treatment session or 2 months post-randomization for participants in the No Treatment condition), and 3-month follow-up.	This is a 6-item measure assessing perceptions of health-related quality of life in adults. It consists of a "descriptive system" and a visual analog scale (VAS). For the descriptive system, the respondent rates five dimensions of their health state on that day - mobility, self-care, usual activities, pain/discomfort, and anxiety/depression - by selecting the most appropriate statement that conveys their level of problem severity in each dimension (no problems, slight problems, moderate problems, severe problems, and extreme problems). Additionally, using the VAS, the respondent rates their overall health on a scale of 0 (worst imaginable health) to 100 (best imaginable health).
Global Impression of Change Scale	Collected via online survey at post-treatment (3 days after last treatment session or 2 months post-randomization for participants in the No Treatment condition).	This is a single-item self-report scale that assesses the perceived intervention-related change in their activity limitations, symptoms, emotions, and overall quality of life via 7-point Likert-type scale. It has been validated in adults with multiple sclerosis.
Global Assessment of Treatment Satisfaction	Collected via online survey at post-treatment (3 days after last treatment session or 2 months post-randomization for participants in the No Treatment condition).	This is a single-item self-report scale that assesses the perceived overall satisfaction with the treatment via 6-point Likert-type scale.
Treatment Recommendation Question	Collected via online survey at post-treatment (3 days after last treatment session or 2 months post-randomization for participants in the No Treatment condition).	This is a single-item self-report that assesses whether a participant would recommend the intervention to a friend with MS fatigue with response options: Yes, No, Unsure, Prefer not to answer.
PROMIS Emotional Distress- Anxiety Short Form 4a	Collected via online survey at baseline/pre-treatment, post-treatment (3 days after last treatment session or 2 months post-randomization for participants in the No Treatment condition), and 3-month follow-up.	This is a 4-item self-report questionnaire assessing symptoms of anxiety via a 5-point Likert-type scale.
PROMIS Pain Interference Short Form 4a	Collected via online survey at baseline/pre-treatment, post-treatment (3 days after last treatment session or 2 months post-randomization for participants in the No Treatment condition), and 3-month follow-up.	This is a 4-item self-report questionnaire assessing pain interference via a 5-point Likert-type scale.
Ecological Momentary Assessment of Fatigue Severity and Interference	Collected via online survey at baseline/pre-treatment, post-treatment (1 day after last treatment session or 2 months post-randomization for participants in the No Treatment condition), and 3-month follow-up.	This is a 6-8-item measure sent 2x/day (morning and evening) for 7 days. It assesses mental and physical fatigue severity and interference on an 11-point numeric rating scale. The morning survey also assesses sleep duration as well as sleep quality via 2 questions rated on a Likert-type scale. The evening survey also assess perceived fatigue management efforts via 2 questions rated on a Likert-type scale.

Trial Locations

Locations (1)

Multiple Sclerosis Center at UW Medical Center - Northwest; 🇺🇸 Seattle, Washington, United States