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Background: Childhood cancer survivors (CCS) have a 50% higher risk of diabetes mellitus (DM) compared with the general population. Interventions in survivors with prediabetes (fasting glucose 100-125 mg/dL or hemoglobin A1c 5.7%-6.4%) may mitigate the development of DM and its attendant morbidity, but there is limited information on the feasibility of secondary prevention in this setting., Methods: This 6-week pilot feasibility 1:1 randomized controlled trial enrolled 20 CCS on a structured telehealth exercise program ± nicotinamide riboside (NR), a nicotinamide adenine dinucleotide precursor. Feasibility metrics were: (1) ≥50% of eligible CCS enrolled onto study; (2) ≥70% of participants completed baseline and end-of-study assessments; (3) ≥70% compliance with exercise and NR. Secondary endpoints included changes in biomarkers associated with glucose homeostasis and muscle health., Results: Median age (years) at cancer diagnosis was 16.5 (range, 1.5-21.5) and 35.5 (range, 18.0-67.0) at study enrollment. Enrollment rate was 87%, and 85% of participants completed baseline and end-of-study assessments. The mean percentage of exercise sessions completed was 86.6%; NR compliance was > 90%. There were no severe adverse events attributable to study interventions. Secondary endpoints were not significantly different between study arms at study completion. Myostatin decrease was observed in participants who completed a higher median number of exercise sessions and was associated with decreased intramuscular adipose tissue and increased lower extremity muscle cross-sectional area., Conclusions: A telehealth exercise intervention ± NR supplementation was feasible in CCS with prediabetes. Future studies in larger cohorts may be needed to evaluate their beneficial effects on muscle health and DM risk among CCS., (© 2024 Wiley Periodicals LLC.)