Protocol for a Sequential Multiple Assignment Randomized Trial to Improve Physical Activity and Diet Quality in...

Survivors of childhood cancer have an increased risk of cardiovascular disease (CVD), but that risk may be reduced by healthy lifestyle behaviors.

Using a sequential multiple assignment randomized trial (SMART) design, this study aims to test different approaches to improve physical activity (PA) and diet quality among long-term survivors of cancer at increased risk of CVD over a 12-month period. The primary study outcomes are sedentary time and Healthy Eating Index (HEI) scores.

Participants were recruited from the Childhood Cancer Survivor Study cohort, with eligibility defined as current age of 18 to 54 years and at least one of three self-reported criteria: (1) <30 minutes per day of moderate to vigorous PA, (2) HEI-2015 score <60, or (3) BMI ≥25 kg/m2. Eligible participants completed baseline surveys, including a food frequency questionnaire, and had PA measured by research-grade accelerometry, and were then randomized to one of three conditions: (1) control, (2) clinician-guided action plan (sessions with the study provider every 2 months), or (3) mobile health-supported goal setting (weekly PA and monthly diet goals based on PA and diet tracker feedback). Following SMART principles, all participants' PA levels and HEI scores were reassessed after 3 months; participants from the 2 intervention groups who did not achieve ≥20-minute per day reduction in sedentary time or a ≥4-point increase in HEI score were classified as nonresponders and rerandomized to the alternative intervention or a more intensive lifestyle coaching intervention (weekly sessions with a study health coach). Intervention participants then entered a less intensive maintenance phase from months 7 to 12. All participants' PA levels and HEI scores were reassessed at 12 months. The target sample size was 375 participants, with 95 participants in the control group and 140 participants in each of the initial intervention groups, which will allow the study to detect changes of 0.35 SD (approximately 30 minutes per day) in sedentary time and 0.41 SD (approximately 4 points) in HEI score between the control and intervention groups (combined). Secondary analyses will test whether there are efficacy differences across intervention strategies, and which intervention sequences are associated with the greatest reduction in sedentary time and improvements in diet quality.

From April 2022 to August 2025, the trial completed recruitment and randomized 374 participants out of 2268 approached. The last participant in this ongoing trial is expected to complete all procedures by the end of 2026, after which the final analyses will be conducted and the results will be reported.

Future findings will inform whether any of these intervention strategies (and/or their combinations) can improve PA levels and diet quality in survivors of cancer at increased risk of CVD.