Background <p>Cancer-related fatigue is one of the most common and debilitating side effects of cancer and its treatments. Fatigue may stem from disruptions in circadian rhythms and dysregulation of glucose metabolism, which can be improved through time-restricted eating. Time-restricted eating is a daily eating pattern that entails consuming food within a defined, consistent window (e.g., 10&#xa0;h) every day. When the eating window aligns with the daylight hours, it can entrain circadian processes and modulate physiological regulation of whole-body metabolism. It is hypothesized that time-restricted eating can relieve cancer-related fatigue in blood cancer survivors via regulating circadian rhythms and improving metabolism.</p> Methods <p>This trial is a phase II randomized controlled trial comparing the effects of time-restricted eating (10&#xa0;h daytime feeding/14&#xa0;h fasting at night) vs. a time-, attention, and expectancy-matched control nutrition counseling intervention (no time component) on cancer-related fatigue. A total of 96 blood cancer survivors will be recruited; eligible survivors will be 2 months to 2 years post-adjuvant chemotherapy, report moderate to severe fatigue, consume food within a window that is &gt; 10&#xa0;h, and not be employed in night-shift work. At baseline, 6 weeks, and 12 weeks (post-intervention), assessments include patient-reported fatigue, measures of circadian rest-activity rhythm, and glucose metabolism via continuous glucose monitoring. Participants will log their food intake using the myCircadianClock smartphone app at baseline and throughout the 12-week study. At 24 weeks (12 weeks post-intervention), questionnaires will probe maintenance of the dietary pattern and sustainability of any intervention effects on fatigue.</p> Discussion <p>Time-restricted eating is scalable and free-of-cost, lending itself to accessibility for the vast majority of cancer survivors. Data generated herein will be used to inform a larger, phase III multisite clinical trial testing the effects of time-restricted eating on cancer-related fatigue among survivors of hematological malignancies, and further optimize interventions that entrain circadian rhythms and improve glucose metabolism to alleviate cancer-related fatigue and other supportive care outcomes.</p> Trial registration <p>clinicaltrials.gov ID: NCT06482515.</p>