Multiple SclerosisNCT06809192
Factorial Optimization Trial to Test Cognitive Behavioral Therapy Components for Multiple Sclerosis Fatigue
A study testing 4-session Relaxation Training, 4-session Behavioral Activation and 4-session Cognitive Therapy in people with Multiple Sclerosis, run by University of Washington at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- 4-session Relaxation Training, 4-session Behavioral Activation and 4-session Cognitive Therapy
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jan 2025to 31 Mar 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed MS diagnosis of any subtype
- Score of 4 or higher on the Fatigue Severity Scale
- Able to fluently converse and read in English
- 18 years of age or older
- Able to comply with study procedures and complete self-report measures
- Willing to have intervention sessions audiotaped for fidelity coding
- Has experienced fatigue for 3 or more months
Who cannot join
- MS relapse within last 30 days (although participants will be considered eligible after the 30-day window)
- Change in disease modifying medications (DMTs) in the prior three months (although participants will be considered eligible after the 3-month window)
- 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)
- Currently engaged in psychotherapy for fatigue
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Multiple Sclerosis Center at UW Medical Center - Northwest
Seattle, Washington, 98133
Study Coordinator, 206-598-0501, cbt-ms-fatigue@uw.edu
Lindsey Knowles, PhD
About this study
Official title: Factorial Optimization Randomized Controlled Trial to Test The Effects of Cognitive Behavioral Therapy Components For Multiple Sclerosis Fatigue
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.
Read the 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.
- Conditions
- Multiple Sclerosis
- Being tested
- 4-session Relaxation Training, 4-session Behavioral Activation, 4-session Cognitive Therapy
- Keywords
- Fatigue, Multiphase Optimization Strategy, Cognitive Behavioral Therapy, Relaxation, Behavioral Activation, Cognitive Therapy, Optimization, Factorial Trial
- Medical subject headings
- Multiple Sclerosis, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4-session Relaxation TrainingBehavioural
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 ActivationBehavioural
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 TherapyBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| No Treatment | No intervention | 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). |
| Relaxation Training only | Experimental | 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. Receives: Behavioral: 4-session Relaxation Training |
| Behavioral Activation only | Experimental | 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. Receives: Behavioral: 4-session Behavioral Activation |
| Cognitive Therapy only | Experimental | 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. Receives: Behavioral: 4-session Cognitive Therapy |
| Relaxation Training and Behavioral Activation | Experimental | 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. Receives: Behavioral: 4-session Relaxation Training; Behavioral: 4-session Behavioral Activation |
| Relaxation Training and Cognitive Therapy | Experimental | 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. Receives: Behavioral: 4-session Relaxation Training; Behavioral: 4-session Cognitive Therapy |
| Behavioral Activation and Cognitive Therapy | Experimental | 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. Receives: Behavioral: 4-session Behavioral Activation; Behavioral: 4-session Cognitive Therapy |
| Relaxation Training, Behavioral Activation, and Cognitive Therapy | Experimental | 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. Receives: Behavioral: 4-session Relaxation Training; Behavioral: 4-session Behavioral Activation; Behavioral: 4-session Cognitive Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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. A higher score indicates greater fatigue.
Measured: 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.
PROMIS Short Form - Ability to Participate in Social Roles and Activities
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.
Measured: 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.
Secondary outcomes (15)
Perceived Stress Questionnaire - Tension scale
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.
Measured: 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.
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. A higher score indicates greater behavioral activation.
Measured: 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.
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. A higher score indicates greater fatigue catastrophizing.
Measured: 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.
The Multiple Sclerosis-Fatigue Self Efficacy Scale
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.
Measured: 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.
Perceived Stress Scale
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.
Measured: 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.
Positive and Negative Affect Schedule
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.
Measured: 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.
PROMIS Emotional Distress-Depression - Short Form 4a
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.
Measured: 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.
EQ-5D-5L
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).
Measured: 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.
Global Impression of Change Scale
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.
Measured: 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).
Global Assessment of Treatment Satisfaction
This is a single-item self-report scale that assesses the perceived overall satisfaction with the treatment via 6-point Likert-type scale.
Measured: 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).
Treatment Recommendation Question
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.
Measured: 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).
PROMIS Emotional Distress- Anxiety Short Form 4a
This is a 4-item self-report questionnaire assessing symptoms of anxiety via a 5-point Likert-type scale.
Measured: 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.
PROMIS Pain Interference Short Form 4a
This is a 4-item self-report questionnaire assessing pain interference via a 5-point Likert-type scale.
Measured: 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.
PROMIS Sleep Disturbance Short Form 4a
This is a 4-item self-report questionnaire assessing sleep disturbance via a 5-point Likert-type scale.
Measured: 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.
Ecological Momentary Assessment of Fatigue Severity and Interference
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2025
- Study start10 Jan 2025
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 112 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Lindsey Knowles, University of Washington
- Investigators
- Lindsey Knowles, PhD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06809192
- Sponsor's protocol ID
- STUDY00021168
- Other IDs
- K23HD111628
- Status last verified
- Mar 2026
- First submitted
- 22 Jan 2025
- Last updated
- 16 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The investigators 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, the investigators 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 the investigators 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 o
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Factorial Optimization Randomized Controlled Trial to Test The Effects of Cognitive Behavioral Therapy Components For Multiple Sclerosis Fatigue
- ClinicalTrials.gov ID
- NCT06809192
- Acronym / sponsor ID
- STUDY00021168
- Conditions
- Multiple Sclerosis
- Keywords
- Fatigue, Multiphase Optimization Strategy, Cognitive Behavioral Therapy, Relaxation, Behavioral Activation, Cognitive Therapy, Optimization, Factorial Trial
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 112 participants (estimated)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 10 Jan 2025 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 5 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| No Treatment | No intervention | –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). |
| Relaxation Training only | Experimental | Behavioral: 4-session Relaxation TrainingA 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 | Experimental | Behavioral: 4-session Behavioral ActivationA 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 | Experimental | Behavioral: 4-session Cognitive TherapyA 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 | Experimental | Behavioral: 4-session Relaxation Training, Behavioral: 4-session Behavioral Activation4 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. |
| Relaxation Training and Cognitive Therapy | Experimental | Behavioral: 4-session Relaxation Training, Behavioral: 4-session Cognitive Therapy4 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. |
| Behavioral Activation and Cognitive Therapy | Experimental | Behavioral: 4-session Behavioral Activation, Behavioral: 4-session Cognitive Therapy4 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. |
| Relaxation Training, Behavioral Activation, and Cognitive Therapy | Experimental | Behavioral: 4-session Relaxation Training, Behavioral: 4-session Behavioral Activation, Behavioral: 4-session Cognitive Therapy4 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Confirmed MS diagnosis of any subtype
- Score of 4 or higher on the Fatigue Severity Scale
- Able to fluently converse and read in English
- 18 years of age or older
- Able to comply with study procedures and complete self-report measures
Key exclusion criteria (5 listed)
- MS relapse within last 30 days (although participants will be considered eligible after the 30-day window)
- Change in disease modifying medications (DMTs) in the prior three months (although participants will be considered eligible after the 3-month window)
- 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)
- Currently engaged in psychotherapy for fatigue
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 4-session Relaxation TrainingA 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. | Behavioural | Relaxation Training and Behavioral Activation, Relaxation Training and Cognitive Therapy, Relaxation Training only, Relaxation Training, Behavioral Activation, and Cognitive Therapy |
| 4-session Behavioral ActivationA 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. | Behavioural | Behavioral Activation and Cognitive Therapy, Behavioral Activation only, Relaxation Training and Behavioral Activation, Relaxation Training, Behavioral Activation, and Cognitive Therapy |
| 4-session Cognitive TherapyA 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. | Behavioural | Behavioral Activation and Cognitive Therapy, Cognitive Therapy only, Relaxation Training and Cognitive Therapy, Relaxation Training, Behavioral Activation, and Cognitive Therapy |
Primary outcome
Modified Fatigue Impact Scale
Time frame: 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
Time frame: 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.
15 secondary outcomes
Perceived Stress Questionnaire - Tension scale
Time frame: 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.
Behavioral Activation for Depression Scale Short Form
Time frame: 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.
Fatigue Catastrophizing Scale
Time frame: 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.
The Multiple Sclerosis-Fatigue Self Efficacy Scale
Time frame: 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.
Perceived Stress Scale
Time frame: 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.
Positive and Negative Affect Schedule
Time frame: 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.
PROMIS Emotional Distress-Depression - Short Form 4a
Time frame: 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.
EQ-5D-5L
Time frame: 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.
Global Impression of Change Scale
Time frame: 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).
Global Assessment of Treatment Satisfaction
Time frame: 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).
Treatment Recommendation Question
Time frame: 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).
PROMIS Emotional Distress- Anxiety Short Form 4a
Time frame: 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.
PROMIS Pain Interference Short Form 4a
Time frame: 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.
PROMIS Sleep Disturbance Short Form 4a
Time frame: 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.
Ecological Momentary Assessment of Fatigue Severity and Interference
Time frame: 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2026.
- Study WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The investigators 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, the investigators 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 the investigators 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 o
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lindsey Knowles, PhD principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 4-session Relaxation Training, 4-session Behavioral Activation and 4-session Cognitive Therapy in people with Multiple Sclerosis, run by University of Washington at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lindsey Knowles, PhD (206-744-9640, lmknow@uw.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Modified Fatigue Impact Scale (time frame: 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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2026; AzTrials last refreshed its copy on 27 Oct 2026.