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.

• 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.]