Time-restricted eating to address cancer-related fatigue among survivors of hematological malignancies

PROJECT SUMMARY Cancer-related fatigue is one of the most common and debilitating toxicities/side effects stemming from cancer and its treatments. Patients who endure hematologic malignancies are disproportionately affected. There are few effective treatments for cancer-related fatigue in part because its underlying etiology and pathophysiology are not well understood. However, disruption of circadian rhythm and dysregulation of glucose metabolism are two related mechanisms that possibly underlie cancer-related fatigue. Time-restricted eating is a daily eating pattern that entails consuming food within a defined, consistent window (e.g., 10 h) every day. When the eating window aligns with the daylight hours, it strongly entrains circadian processes and modulates 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 rhythm and improving metabolism. This project is a 12- week, two-arm, phase II randomized controlled trial comparing the effects of time-restricted eating (10 h daytime feeding/14 h fasting at night) vs. a control, unrestricted feeding arm on cancer-related fatigue; follow-up at 24 weeks is also planned. A total of 96 blood cancer survivors will be recruited; eligible survivors will be 2 months to 2 years post-curative treatment, suffer from moderate to severe fatigue, consume food within a window that is >10 h, and not be employed away from the home at night. They will be randomized 1:1, intervention: control. All participants will meet with a nutritionist and discuss nutrition guidelines for cancer survivors; those in the intervention group will self-select a 10-hour eating window in which to meet the guidelines. At baseline, 6 weeks, and 12 weeks (post-intervention), we will assess patient-reported fatigue, measures of circadian activity rhythm (via an activity tracker) 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. Aim 1 is to provide initial estimates of efficacy of the 12-week time-restricted eating intervention vs. an unrestricted eating pattern on patient-reported fatigue. Aim 2 is to assess maintenance of the dietary pattern and sustainability of any changes in fatigue at 24 weeks. Mechanistic aims assess the effects of time-restricted eating on circadian rest-activity rhythm (mesor, amplitude, and acrophase) and glucose metabolism (fasting blood glucose, average blood glucose, glucose excursions), specifically exploring: 1) the associations between changes in circadian rhythms, glucose metabolism, and fatigue from baseline to post-intervention, and 2) the associations between adherence to the intervention and changes in circadian rhythm, glucose metabolism, and fatigue. The time- restricted eating intervention is scalable and inexpensive, lending itself to be accessible to most 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 rhythm and improve glucose metabolism to alleviate cancer-related fatigue.