Decreasing Cardiometabolic Risk in Survivors of Childhood Cancer: Survivors engaged in Time-Restricted EatiNG after THerapy (STRENGTH)

PROJECT SUMMARY Over 500,000 survivors of childhood cancer are living in the United States today. Cardiovascular disease is the leading cause of noncancer late mortality in this cohort. Subgroups of survivors, including individuals previously exposed to radiation to the chest, abdomen, and total body, are also at treatment-related risk for a

constellation of cardiometabolic comorbidities, including type 2 diabetes mellitus, chronic inflammation, and hypertension, which further amplifies their risk of cardiovascular disease. Tailored, scalable and sustainable interventions that target modifiable risk factors, such as obesity, are thus urgently needed to reduce

cardiometabolic risk in this cohort. Time-restricted eating, or voluntary abstinence from all caloric intake for 14- 16 hours per day, has been demonstrated in pre-clinical and human studies to combat these risks. This mode of fasting appears to be feasible, safe, and sustainable in diverse populations. Results on the efficacy of time-

restricted eating, however, are discrepant across studies, with some studies demonstrating marked improvement in weight, glycemic control, and circadian rhythm alignment and others showing minimal effect. Yet this intervention has not been tested in childhood cancer survivors, and it is unknown whether it would be

an efficacious risk-reducing intervention in this population. The proposed STRENGTH (Survivors engaged in Time-Restricted EatiNG after THerapy) Study would fill this gap by determining the efficacy of time-restricted eating to reduce weight and improve markers of cardiometabolic risk in radiation-exposed survivors with

overweight/obesity. To this end, we will conduct a phase IIb randomized controlled trial of 300 radiation- exposed survivors of childhood cancer with overweight/obesity and enrolled in the Childhood Cancer Survivor Study (CCSS). Participants will be randomized to either a 6-month time-restricted eating intervention followed

by a 6-month maintenance phase, or usual care, which consists of mailed educational handouts on healthy lifestyle behaviors. We will: (1) Determine the impact of time-restricted eating on measures of weight status and other weight-related outcomes (waist circumference, percent body fat); (2) Assess the impact of time-

restricted eating on cardiometabolic risk profile (blood pressure, glycemic control, insulin resistance, adipokines, markers of inflammation); (3) Identify moderating and mediating factors, as well as barriers and facilitators, associated with adherence to the intervention and weight loss, with the goal of informing future

implementation efforts. The proposed time-restricted eating intervention, which is grounded in social cognitive theory, will include stepwise progression to build self-efficacy using “nudges” and motivational interviewing. This proposal will leverage novel mHealth technology to deliver a fully remote, theoretically grounded

behavioral intervention to reduce cardiometabolic risk and thereby address the burdens of cancer and its treatment among adult-aged survivors of childhood cancer. Time-restricted eating may represent a sustainable intervention to improve long-term outcomes in a highly morbid survivor cohort.