Project Summary/Abstract: Lindsey Knowles, PhD is a psychologist and postdoctoral fellow in the University of Washington (UW) and VA Puget Sound Health Care System (VAPSHCS) Seattle Collaborative Fellowship in Multiple Sclerosis (MS) Rehabilitation Research. She is fully committed to becoming an independently funded investigator who develops, optimizes, and evaluates theory-driven, implementable interventions to improve symptoms, psychosocial function, and quality of life in adults with chronic health conditions/disability. Dr. Knowles is an ideal candidate for this field of research given her strong background in observational and intervention research on stress and coping and advanced fellowship training in rehabilitation research. This K23 award will provide foundational career development skills for achieving her long-term goal of optimizing evidence-based and accessible treatment for improving symptoms, function, and quality of life in people with chronic health conditions. The proposed project will develop, refine, and optimize a telehealth Cognitive Behavioral Therapy (CBT) intervention for fatigue in people with MS (PwMS). Findings will support a randomized controlled trial to evaluate the optimized CBT-based intervention for MS fatigue. Career Development and Training Plan: The proposed work will be carried out at the UW and utilize resources within the UW Department of Rehabilitation Medicine and VAPSHCS MS Center of Excellence West. Dr. Knowles’s distinguished mentorship team includes Drs. Dawn Ehde (Primary Mentor; telehealth CBT and MS expert), Aaron Turner (MS behavioral intervention expert), Linda Collins [Multiphase Optimization Strategy (MOST) expert], and Anna Kratz (qualitative research expert). Dr. Knowles’s training goals align her research and career plans via didactic and hands-on training in: (1) Intervention optimization and clinical trials methods via MOST, (2) Rapid qualitative research methods, and (3) Proficiency in grantsmanship and scientific dissemination. Research Plan: The proposed aims will address a gap in knowledge related to the active ingredients of CBT for improving MS fatigue. This knowledge will facilitate optimization of CBT for MS fatigue to maximize efficacy and efficiency, thereby improving implementation and accessibility. The study aims are to (1) Develop, pilot test, and refine three telehealth CBT components for fatigue in PwMS (Relaxation Training, Behavioral Activation, Cognitive Therapy) to maximize feasibility and acceptability; (2a) Conduct component analysis (via factorial optimization trial) to test the main and interactive effects of the three telehealth CBT components for improving fatigue and psychosocial function in fatigued PwMS (primary outcomes); (2b) Assess change in hypothesized unique and common mechanisms of the three telehealth CBT components; (2c) Evaluate the durability of outcome improvements through the 3-month follow-up. Components will be selected for an optimized interven...