Cancer
Conditions
Keywords
Time-restricted eating, Time restricted eating, Meal timing
Brief summary
The goal of this clinical trial is to test meal-timing as a novel and sustainable interventional approach during cancer treatment to improve therapeutic response, patient well-being and long-term metabolic health. In alignment with these priorities, we propose to focus on patients with histologically or cytologically confirmed solid tumors treated with curative-intent surgical resection and planned initiation of systemic adjuvant therapy (chemotherapy, targeted therapy, immunotherapy, and/or radiation per standard of care). A promising strategy for improving the efficacy of anticancer treatments and reducing associated toxicities involves combining treatment with fasting regimens. In pre-clinical and clinical studies, various forms of fasting have been shown to induce tumor regression and improve long-term survival. According to the differential stress sensitization theory, fasting is thought to sensitize tumor cells to the cytotoxic effects of chemotherapy and radiation, while protecting healthy cells by increasing stress resistance. While healthy cells slow their growth and become more stress resistant in response to fasting, cancer cells cannot survive in nutrient-deficient environments; although the underlying mechanisms are not fully understood. However, extended water-only fasting can be challenging for patients and poses undue health risks. Intermittent fasting, and specifically time-restricted eating (TRE), may offer a viable alternative. TRE involves eating within a shorter window (e.g., 8 hours) and fasting for the remainder of the day but involves no other dietary restrictions. Because of its simplicity, TRE may be more sustainable than other fasting regimens. TRE also improves several cardio-metabolic endpoints, including insulin sensitivity, which may also be beneficial during anticancer treatments.
Detailed description
Participants will be randomized to one of two groups: 1. Time-restricted eating (TRE) (8-hour daily eating period, starting 1-3 hours after waking up), OR 2. 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.
Interventions
BEHAVIORALTime-restricted eating
Participate in time-restricted eating plan
OTHERQuestionnaire Administration
Complete questionnaire
PROCEDUREBiospecimen Collection
Undergo collection of blood and stool
BEHAVIORALHealth coaching
Receive nutrition counseling
Sponsors
Fred Hutchinson Cancer Center
National Cancer Institute (NCI)
Alaska Native Tribal Health Consortium
Alaska Native Medical Center
Cedars-Sinai Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years (no upper age limit) * Any sex or gender * Histologically or cytologically confirmed solid tumor treated with curative-intent surgical resection and planned initiation of systemic adjuvant therapy (chemotherapy, targeted therapy, immunotherapy, and/or radiation per standard of care) * BMI ≥18.5 kg/m2 * Willing and able to adhere to the assessments, visit schedules, prohibitions, and restrictions
Exclusion criteria
* No plan for systemic adjuvant therapy after surgery * Strictly adhering to a \<10-hour eating window on most days * Regular overnight shift work (≥1 night shift per week) * Dependent on parenteral or enteral nutrition * Pregnant or breastfeeding * Active second malignancy requiring systemic therapy (exceptions: non-melanoma skin cancers or in situ cervical cancers adequately treated) * Severe psychiatric, cognitive, or social conditions that would interfere with adherence to study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient-reported treatment-related toxicities: Average weekly scores | Assessed weekly from start of intervention through end of intervention (up to approximately 6 months) | Assessed via Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE v5) toxicities, which is administered weekly throughout intervention and therapy; average scores calculated at each time point, timed to oncologic treatment cycles. |
| Treatment Delivery: Relative dose intensity (RDI) | At end of intervention (at approximately 6 months) | Relative dose intensity (RDI), defined as delivered/planned dose intensity, will be analyzed both as a continuous outcome (% of delivered vs planned) and as a binary outcome (≥85% vs. \< 85%). Regimen-level RDI will be calculated as the average across drugs or based on the dose-limiting agent. |
| Treatment Delivery: Number of patients completing planned adjuvant therapy without unplanned dose reductions or delays | At end of intervention (at approximately 6 monhts) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinician-reported CTCAE grade ≥3 toxicities | Baseline through end of intervention (at approximately 6 months) | — |
| Clinician-reported Toxicity Index | Baseline through end of intervention (at approximately 6 months) | — |
| Changes in quality of life (QOL): EORTC QLQ-C30 | Baseline (within 28 days prior to initiation of adjuvant therapy), approximately 2-3 months after treatment initiation, end of treatment (within 6 weeks after completion of adjuvant therapy), and follow-up (6-12 months after completion of treatment) | Change in quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), a validated 30-item instrument measuring global health status/quality of life, functional domains (physical, role, emotional, cognitive, and social functioning), and symptom domains. Scores are linearly transformed to a 0-100 scale according to standard scoring guidelines. For global health status and functional scales, higher scores indicate better functioning or quality of life; for symptom scales, higher scores indicate greater symptom burden. |
| PROMIS Anxiety | Baseline (within 28 days prior to initiation of adjuvant therapy), approximately 2-3 months after treatment initiation, end of treatment (within 6 weeks after completion of adjuvant therapy), and follow-up (6-12 months after completion of treatment) | Change in anxiety measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety short form. Scores are standardized T-scores (mean = 50, standard deviation = 10). Higher scores indicate greater anxiety. |
| PROMIS Fatigue | Baseline (within 28 days prior to initiation of adjuvant therapy), approximately 2-3 months after treatment initiation, end of treatment (within 6 weeks after completion of adjuvant therapy), and follow-up (6-12 months after completion of treatment) | Change in fatigue measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue short form. Scores are standardized T-scores (mean = 50, standard deviation = 10). Higher scores indicate greater fatigue. |
| PROMIS Physical Function | Baseline (within 28 days prior to initiation of adjuvant therapy), approximately 2-3 months after treatment initiation, end of treatment (within 6 weeks after completion of adjuvant therapy), and follow-up (6-12 months after completion of treatment) | Change in physical function measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function short form. Scores are standardized T-scores (mean = 50, standard deviation = 10). Higher scores indicate better physical function. |
| UCLA Loneliness Scale | Baseline (within 28 days prior to initiation of adjuvant therapy), approximately 2-3 months after treatment initiation, end of treatment (within 6 weeks after completion of adjuvant therapy), and follow-up (6-12 months after completion of treatment) | Change in perceived loneliness assessed using the UCLA Loneliness Scale. Scores are calculated by summing item responses, with higher scores indicating greater perceived loneliness. |
| Munich Chronotype Questionnaire (MCTQ) | Baseline (within 28 days prior to initiation of adjuvant therapy), approximately 2-3 months after treatment initiation, end of treatment (within 6 weeks after completion of adjuvant therapy), and follow-up (6-12 months after completion of treatment) | Change in chronotype assessed using the Munich Chronotype Questionnaire. Chronotype is derived as mid-sleep time on free days, corrected for sleep debt (MSFsc), with later times indicating more evening preference. |
| Pittsburgh Sleep Quality Index (PSQI) | Baseline (within 28 days prior to initiation of adjuvant therapy), approximately 2-3 months after treatment initiation, end of treatment (within 6 weeks after completion of adjuvant therapy), and follow-up (6-12 months after completion of treatment) | Change in sleep quality assessed using the Pittsburgh Sleep Quality Index (PSQI). The global score is calculated from seven components, with higher scores indicating poorer sleep quality. |
| Appetite Questionnaire | Baseline (within 28 days prior to initiation of adjuvant therapy), approximately 2-3 months after treatment initiation, end of treatment (within 6 weeks after completion of adjuvant therapy), and follow-up (6-12 months after completion of treatment) | Change in appetite assessed using a validated appetite questionnaire. Scores reflect patient-reported appetite levels, with higher scores indicating greater appetite (or specify direction if opposite). |
| Dutch Eating Behavior Questionnaire (DEBQ) | Baseline (within 28 days prior to initiation of adjuvant therapy), approximately 2-3 months after treatment initiation, end of treatment (within 6 weeks after completion of adjuvant therapy), and follow-up (6-12 months after completion of treatment) | Change in eating behaviors assessed using the Dutch Eating Behavior Questionnaire (DEBQ), including emotional eating, external eating, and restrained eating subscales. Higher scores indicate greater endorsement of the respective eating behavior. |
| Fasting Insulin | Baseline (within 28 days prior to initiation of adjuvant therapy), approximately 2-3 months after treatment initiation, end of treatment (within 6 weeks after completion of adjuvant therapy), and follow-up (6-12 months after completion of treatment) | Change in fasting insulin levels measured from blood samples |
| Fasting Glucose | Baseline (within 28 days prior to initiation of adjuvant therapy), approximately 2-3 months after treatment initiation, end of treatment (within 6 weeks after completion of adjuvant therapy), and follow-up (6-12 months after completion of treatment) | Change in fasting glucose levels measured from blood samples. |
| IGF-1 | Baseline (within 28 days prior to initiation of adjuvant therapy), approximately 2-3 months after treatment initiation, end of treatment (within 6 weeks after completion of adjuvant therapy), and follow-up (6-12 months after completion of treatment) | Change in circulating IGF-1 levels measured from blood samples. |
| Total Cholesterol | Baseline (within 28 days prior to initiation of adjuvant therapy), approximately 2-3 months after treatment initiation, end of treatment (within 6 weeks after completion of adjuvant therapy), and follow-up (6-12 months after completion of treatment) | Change in total cholesterol levels measured from blood samples. |
| LDL Cholesterol | Baseline (within 28 days prior to initiation of adjuvant therapy), approximately 2-3 months after treatment initiation, end of treatment (within 6 weeks after completion of adjuvant therapy), and follow-up (6-12 months after completion of treatment) | Change in low-density lipoprotein (LDL) cholesterol levels measured from blood samples. |
| HDL Cholesterol | Baseline (within 28 days prior to initiation of adjuvant therapy), approximately 2-3 months after treatment initiation, end of treatment (within 6 weeks after completion of adjuvant therapy), and follow-up (6-12 months after completion of treatment) | Change in high-density lipoprotein (HDL) cholesterol levels measured from blood samples. |
| Triglycerides | Baseline (within 28 days prior to initiation of adjuvant therapy), approximately 2-3 months after treatment initiation, end of treatment (within 6 weeks after completion of adjuvant therapy), and follow-up (6-12 months after completion of treatment) | Change in triglyceride levels measured from blood samples. |
| C-Reactive Protein (CRP) | Baseline (within 28 days prior to initiation of adjuvant therapy), approximately 2-3 months after treatment initiation, end of treatment (within 6 weeks after completion of adjuvant therapy), and follow-up (6-12 months after completion of treatment) | Change in CRP levels measured from blood samples as a marker of systemic inflammation. |
| Vitamin D | Baseline (within 28 days prior to initiation of adjuvant therapy), approximately 2-3 months after treatment initiation, end of treatment (within 6 weeks after completion of adjuvant therapy), and follow-up (6-12 months after completion of treatment) | Change in circulating 25-hydroxyvitamin D levels measured from blood samples. |
| Changes in sleep and physical activity patterns measured by wrist actigraphy | Baseline and end of treatment (approximately 6 months) | Sleep and physical activity patterns will be assessed using wrist actigraphy to measure parameters such as sleep duration, sleep timing, sleep efficiency, and activity levels. |
| Change in gut microbiome composition and diversity from stool samples | Baseline, mid-treatment (approximately 3 months), and end of treatment (approximately 6 months) | Change in stool-derived gut microbiome composition, including relative abundance of microbial taxa, and microbial diversity indices (e.g., alpha diversity such as Shannon index), measured using sequencing-based methods (e.g., 16S rRNA sequencing and metagenomics). |
| Changes in glucose patterns measured using continuous glucose monitoring (CGM) | Baseline and end of treatment (approximately 6 months) | Glucose levels will be continuously monitored using a wearable continuous glucose monitor to assess changes in glycemic patterns associated with the intervention. |
Countries
United States
Contacts
CONTACTJane Figueiredo, PhD
PRINCIPAL_INVESTIGATORJane Figueiredo, PhD
Cedars-Sinai Medical Center
PRINCIPAL_INVESTIGATORTimothy Thomas, MD
Alaska Native Tribal Health Consortium (ANTHC)
Outcome results
None listed