Smartphone-Based Physical Activity Program to Reduce "Chemo-Brain" Symptoms and Improve Health in Cancer Survivors With and Without Type 2 Diabetes: Protocol for a Single-Arm Pre-Post Pilot Trial

Abstract

Background: The US cancer survivor population is projected to hit 26M by 2040. Chemotherapy is an effective cancer treatment, but can diminish cancer survivors’ quality of life—particularly cognitive function—through select pathophysiological processes, including immune system and antioxidant dysregulation. The resulting cytokine release can impair cerebrovascular function—likely contributing to chemotherapy-induced cognitive impairment (CICI; “chemo-brain”). Type 2 diabetes mellitus (T2DM)—a common cancer survivor comorbidity—shares underlying pathophysiology with CICI. Cancer survivors with T2DM might thus have a higher CICI risk than those without T2DM. Physical activity (PA) counteracts CICI’s and T2DM’s pathophysiology, but little to no research has been conducted assessing the impact of PA on this joint pathophysiology. Objective: To compare cerebrovascular and cognitive function as well as proinflammatory, cardiometabolic, epigenetic, and psychosocial outcomes between ancer survivors with and without T2DM pre- to postengagement in a 12-week technology-based PA program grounded in the Social Cognitive Theory. We hypothesize that cancer survivors with and without T2DM will demonstrate similar pre to poststudy improvements in psychosocial outcomes, but that changes in cerebrovascular and cardiometabolic outcomes, as well as PA engagement, will be greater for cancer survivors with T2DM. We also believe that each group will have distinct epigenetic profiles that will change pre to poststudy. Methods: We are conducting a 30-participant pilot study in cancer survivors with (n=15) and without (n=15) T2DM—all of whom report currently experiencing “chemo-brain.” To account for attrition, we are recruiting 38 cancer survivors from Oklahoma City, OK, and the surrounding area. Among the most important eligibility criteria are the self-report of cognitive difficulties following primary cancer treatment, being ≥18 years old, being within 3 years of primary cancer treatment, and not meeting nationally recommended PA guidelines. Participants receive 2 smartphone apps. One smartphone app provides health education and the ability to set goals and journal about their wellness journey. The other provides a workout program continually tailored to each participant via their communication with the study exercise physiologist, with resistance bands and a wearable device provided to support the program. At Baseline and Poststudy, we assess cerebrovascular function (transcranial doppler [TCD]), cognition (National Institutes of Health Toolbox), cardiometabolic outcomes (venipuncture), and epigenetics (saliva collection). Participants also wear accelerometers at Baseline and Poststudy to objectively assess PA, with Baseline, Midpoint, and Poststudy surveys assessing psychosocial outcomes. We will use t tests and chi-square tests to assess baseline differences and repeated-measures ANCOVA to assess changes over time. Results: Participant recruitment started in March 2025, and we expect to recruit until late 2026. We will begin analyzing baseline data in 2026. Conclusions: Successful study completion will provide valuable insights into the remote delivery of PA-oriented supportive care for cancer survivors experiencing chemo-brain, as well as how T2DM and PA contribute to the mechanistic underpinnings of chemo-brain.