Effect of Meal Timing During Cancer Treatment in Patients in Alaska: A Randomized Clinical Trial

Participants will be randomized to one of two groups:

• Time-restricted eating (TRE) (8-hour daily eating period, starting 1-3 hours after waking up), OR
• A control group defined as a ≥12-hour daily eating period.

Participants are assigned to either TRE (8-hour daily eating period, starting 1-3 hours after waking up) or a control group defined as a ≥12-hour daily eating period. Their randomized meal assignment arm begins no later than 1-2 week after they begin cancer treatment and ends at end of treatment (resection if indicated). This is a period of approximately 6 months.

During this time, participants will be asked to record the time they started and finished eating every day. Electronic reminders and weekly calls to the participants will be made by study staff who maintain records of patient's meal timing. Researchers will time the TRE schedules relative to sleep time (not time of day), which is a reasonable proxy for circadian time. The control group was designed to mimic typical eating habits in the U.S., as data from NHANES suggest that the median American eats over a 12.5-hour period each day. Aside from these general prescriptions, no set number of snacks, meals, or calories will be prescribed. Instead, researchers will measure how TRE affects self-reported mealtimes, meal frequency, and food intake through a combination of daily adherence surveys, 3-day food records and continuous glucose monitoring (CGM).

Participants will receive weekly one-on-one nutrition counseling during the first month and then monthly counseling sessions thereafter. Participants will complete questionnaires at intake and subsequent follow-up assessments. Blood and stool samples will also be collected from participants throughout the study.

Inclusion criteria

• Male or female
• Self-identify as Alaska Native or American Indian person and eligible for care at the ANMC
• Age≥21 years
• Histologically confirmed rectal cancer stage II, III, or IV (if curative) per AJCC criteria (neoadjuvant)
• Histologically confirmed HER2+ or triple negative breast cancer stage I, II, or III, per AJCC criteria (neoadjuvant)
• Histologically or cytologically confirmed solid tumor (adjuvant)
• BMI≥18.5 kg/m2
• Plan to receive neoadjuvant or adjuvant therapy
• Planned duration of neoadjuvant or systemic adjuvant therapy for >3 months to allow sufficient time to assess impact of intervention
• Must have capacity to give informed consent
• Willing and able to adhere to the assessments, visit schedules, prohibitions, and restrictions
• Has completed ≤ 4 weeks of neoadjuvant or adjuvant treatment prior to study enrollment
• Score of < 4 on U.S. Household Food Security Survey Module: Six-Item Short Form OR if score >5, have clearance from dietitian

Exclusion criteria

• History of cytotoxic chemotherapy ≤12 months prior to rectal or breast cancer diagnosis (neoadjuvant)
• Allergic reaction to any of the treatment agents
• Any prior pelvic radiotherapy
• Active second malignancy (exceptions: non-melanoma skin cancers or cervical carcinoma in situ adequately treated) requiring systemic therapy
• History of GI perforation ≤12 months prior to enrollment
• History of predisposing colonic or small bowel disorders with severe or rapidly worsening symptoms (not related to current cancer symptoms)
• Receiving any parenteral nutrition or enteral (tube) feeding or using similar nutritional supplement during the study period
• History of uncontrolled CHF defined as NYHA Class III or greater
• Pre-existing grade ≥3 neuropathy
• Currently participating in or has participated in a study of an investigational agent or investigational device ≤4 weeks of the first dose of treatment
• Unstable psychiatric, sleep, or circadian conditions (common conditions such as sleep apnea and depression are acceptable as long as they are stabilized and not rapidly worsening)
• Pregnant or breastfeeding
• Currently perform overnight shift work >1 day/week
• Strictly adhering to a <10-hour eating window on most days
• Severe psychiatric, cognitive, or substance misuse disorders or social conditions that would interfere with adherence to study procedures.