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

NCT ID: NCT06809192

Last Updated: 2025-03-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

112 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-01-10

Study Completion Date

2027-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Multiple Sclerosis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

No Treatment

Participants in the "No Treatment" condition will not complete any component sessions and will complete assessments at baseline (within 1 month of randomization), at approximately 2 months after randomization (the weighted average of weeks of treatment in the other conditions), and 3-month follow-up (dated from randomization). Upon study completion, these participants will be offered the opportunity to complete a component of their choice (Relaxation Training, Behavioral Activation, or Cognitive Therapy).

Group Type NO_INTERVENTION

No interventions assigned to this group

Relaxation Training only

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, c) didactic and experiential training in relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, and autogenic relaxation, and d) goal setting and problem-solving barriers to integrate relaxation practices into daily routine.

Group Type EXPERIMENTAL

4-session Relaxation Training

Intervention Type BEHAVIORAL

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, c) didactic and experiential training in relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, and autogenic relaxation, and d) goal setting and problem-solving barriers to integrate relaxation practices into daily routine.

Behavioral Activation only

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.

Group Type EXPERIMENTAL

4-session Behavioral Activation

Intervention Type BEHAVIORAL

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.

Cognitive Therapy only

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, c) labeling thoughts as helpful, unhelpful, or neutral, d) using distraction to cope with unhelpful thoughts, e) challenging and changing unhelpful thoughts, f) problem-solving barriers to coping with or changing unhelpful thoughts.

Group Type EXPERIMENTAL

4-session Cognitive Therapy

Intervention Type BEHAVIORAL

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, c) labeling thoughts as helpful, unhelpful, or neutral, d) using distraction to cope with unhelpful thoughts, e) challenging and changing unhelpful thoughts, f) problem-solving barriers to coping with or changing unhelpful thoughts.

Relaxation Training and Behavioral Activation

4 sessions of telehealth Relaxation Training and 4 sessions of telehealth Behavioral Activation for multiple sclerosis fatigue that are derived from evidence-based multicomponent CBT for multiple sclerosis fatigue. Each intervention involves 4, 30-60-minute sessions delivered via phone or videoconference.

Group Type EXPERIMENTAL

4-session Relaxation Training

Intervention Type BEHAVIORAL

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, c) didactic and experiential training in relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, and autogenic relaxation, and d) goal setting and problem-solving barriers to integrate relaxation practices into daily routine.

4-session Behavioral Activation

Intervention Type BEHAVIORAL

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.

Relaxation Training and Cognitive Therapy

4 sessions of telehealth Relaxation Training and 4 sessions of telehealth Cognitive Therapy for multiple sclerosis fatigue that are derived from evidence-based multicomponent CBT for multiple sclerosis fatigue. Each intervention involves 4, 30-60-minute sessions delivered via phone or videoconference.

Group Type EXPERIMENTAL

4-session Relaxation Training

Intervention Type BEHAVIORAL

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, c) didactic and experiential training in relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, and autogenic relaxation, and d) goal setting and problem-solving barriers to integrate relaxation practices into daily routine.

4-session Cognitive Therapy

Intervention Type BEHAVIORAL

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, c) labeling thoughts as helpful, unhelpful, or neutral, d) using distraction to cope with unhelpful thoughts, e) challenging and changing unhelpful thoughts, f) problem-solving barriers to coping with or changing unhelpful thoughts.

Behavioral Activation and Cognitive Therapy

4 sessions of telehealth Behavioral Activation and 4 sessions of telehealth Cognitive Therapy for multiple sclerosis fatigue that are derived from evidence-based multicomponent CBT for multiple sclerosis fatigue. Each intervention involves 4, 30-60-minute sessions delivered via phone or videoconference.

Group Type EXPERIMENTAL

4-session Behavioral Activation

Intervention Type BEHAVIORAL

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.

4-session Cognitive Therapy

Intervention Type BEHAVIORAL

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, c) labeling thoughts as helpful, unhelpful, or neutral, d) using distraction to cope with unhelpful thoughts, e) challenging and changing unhelpful thoughts, f) problem-solving barriers to coping with or changing unhelpful thoughts.

Relaxation Training, Behavioral Activation, and Cognitive Therapy

4 sessions of telehealth Relaxation Training, 4 sessions of telehealth Behavioral Activation, and 4 sessions of telehealth Cognitive Therapy for multiple sclerosis fatigue that are derived from evidence-based multicomponent CBT for multiple sclerosis fatigue. Each intervention involves 4, 30-60-minute sessions delivered via phone or videoconference.

Group Type EXPERIMENTAL

4-session Relaxation Training

Intervention Type BEHAVIORAL

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, c) didactic and experiential training in relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, and autogenic relaxation, and d) goal setting and problem-solving barriers to integrate relaxation practices into daily routine.

4-session Behavioral Activation

Intervention Type BEHAVIORAL

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.

4-session Cognitive Therapy

Intervention Type BEHAVIORAL

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, c) labeling thoughts as helpful, unhelpful, or neutral, d) using distraction to cope with unhelpful thoughts, e) challenging and changing unhelpful thoughts, f) problem-solving barriers to coping with or changing unhelpful thoughts.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

4-session 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, c) didactic and experiential training in relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation, and autogenic relaxation, and d) goal setting and problem-solving barriers to integrate relaxation practices into daily routine.

Intervention Type BEHAVIORAL

4-session 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.

Intervention Type BEHAVIORAL

4-session 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, c) labeling thoughts as helpful, unhelpful, or neutral, d) using distraction to cope with unhelpful thoughts, e) challenging and changing unhelpful thoughts, f) problem-solving barriers to coping with or changing unhelpful thoughts.

Intervention Type BEHAVIORAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Lindsey Knowles

Assistant Professor, Department of Rehabilitation Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Lindsey Knowles, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Multiple Sclerosis Center at UW Medical Center - Northwest

Seattle, Washington, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Lindsey Knowles, PhD

Role: CONTACT

206-744-9640

Dawn Ehde, PhD

Role: CONTACT

206-744-2811

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Study Coordinator

Role: primary

206-598-0501

Related Links

Access external resources that provide additional context or updates about the study.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

K23HD111628

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00021168

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Memory Flexibility Training for Depression
NCT02371291 COMPLETED PHASE1/PHASE2