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, and epigenetic 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).

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 being insufficiently active. All participants receive two smartphone applications. One smartphone application provides health education messaging and a place for participants to draft health and wellness goals and journal about their wellness journey. The other smartphone application provides access to a workout program that is continually tailored to each participant via their communication with the study’s exercise physiologist, with participants provided resistance bands and a wearable device. At Baseline and Post-Study, we are assessing cerebrovascular function using transcranial doppler measurements at rest and during exercise. Cognitive function is being assessed using the NIH Toolbox, and cardiometabolic and epigenetic outcomes are being assessed via blood and saliva collection. Further, at Baseline, Midpoint, and Post-Study, we are assessing SCT-related constructs as well as stress/anxiety symptoms, mood, and QoL. Finally, for seven days before and immediately after the 12-week technology-based PA program, we are assessing PA using ActiGraph accelerometers. We will use t-tests and chi-squared tests to assess baseline differences and repeated-measures ANCOVA to assess changes over time.

Results:

We started recruiting CS in March 2025, and we expect to recruit participants until June 2026. We will begin analyzing baseline data in early 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