JMIR Publications

ABSTRACT

Background:

The U.S. cancer survivor (CS) population is projected to hit 26M by 2040. Chemotherapy is an effective cancer treatment but can diminish CS quality of life (QoL)—particularly cognitive function—through select pathophysiological processes, including immune system and antioxidant dysregulation. The resulting cytokine release can damage cerebrovascular function—likely contributing to chemotherapy-induced cognitive impairment (CICI; ‘chemo-brain’). Type 2 diabetes mellitus (T2DM)—a common CS comorbidity—shares underlying pathophysiology with CICI. CS with T2DM might thus have 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 pro-inflammatory, cardiometabolic, epigenetic, and psychosocial outcomes between CS with and without T2DM pre- to post-engagement in a 12-week technology-based PA program grounded in the Social Cognitive Theory (SCT). We hypothesize that CS with and without T2DM will demonstrate similar pre- to post-study improvements in psychosocial outcomes but that changes in cerebrovascular and cardiometabolic outcomes, as well as PA engagement, will be greater for CS with T2DM. We also believe that each group will have distinct epigenetic profiles that will change pre- to post-study.

Methods:

We are conducting a 30-participant pilot study in CS with (n=15) and without (n=15) T2DM—all of whom report currently experiencing ‘chemo-brain’. To account for attrition, we are recruiting 38 CS 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 three years of primary cancer treatment, and not meeting nationally recommended PA guidelines. Participants receive two smartphone applications. One smartphone application 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 Post-Study, we assess cerebrovascular function (transcranial doppler), cognition (NIH Toolbox), cardiometabolic outcomes (venipuncture), and epigenetics (saliva collection). Participants also wear accelerometers at Baseline and Post-Study to objectively assess PA, with Baseline, Midpoint, and Post-Study surveys assessing psychosocial outcomes. We will use t-tests and chi-squared 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 CS experiencing chemo-brain as well as how T2DM and PA contribute to the mechanistic underpinnings of chemo-brain. Clinical Trial: NCT06725953