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

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.

Inclusion criteria

• 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

Exclusion criteria

• 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)