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Time-Restricted Eating and Cancer: Clinical Outcomes, Mechanisms, and Moderators

Primary Purpose

Colorectal Cancer

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Time-Restricted Eating (TRE)

Control

About this trial

This is an interventional treatment trial for Colorectal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female of any ethnic/racial background
Age 21 years or older
Histologically confirmed rectal cancer stage II or III per AJCC criteria
BMI 18.5 kg/m2 or greater
Plan to receive either neoadjuvant conventional chemoradiation or total neoadjuvant therapy (TNT) with 5-fluorouracil-based regimens
Demonstrate adequate organ and marrow function within two weeks of study treatment initiation
Willing and able to adhere to the assessments, visit schedules, prohibitions, and restrictions

Exclusion Criteria:

Prior neoadjuvant or adjuvant chemotherapy/radiation <12 months prior to rectal cancer occurrence
Allergic reaction to any of the treatment agents
Any prior pelvic radiotherapy or chemoradiotherapy
Major surgery/open biopsy ≤4 weeks prior to enrollment or minor surgery/core biopsy ≤1 week prior to enrollment
Currently active second malignancy other than non-melanoma skin cancers or cervical carcinoma in situ
History of GI perforation ≤12 months prior to enrollment
History of malabsorption, uncontrolled vomiting or diarrhea, or other GI-function affecting disease
History of predisposing colonic or small bowel disorders with uncontrolled symptoms
Receiving any parenteral nutrition or enteral (tube) feeding or using any other nutritional supplement during the study period
History of uncontrolled CHF defined as NYHA Class III or greater
Uncontrolled hypertension
History of bleeding events, bleeding diathesis, arterial thrombotic events (including TIA, CVA, unstable angina requiring intervention, or MI), or clinically significant PAD and ≤6 months prior to enrollment
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 more than one day/week on average
Regularly eat within an <11-hour period each day
Will travel more than three time zones away during the study
Known psychiatric or substance abuse disorders that would interfere with adhering to the requirements of the trial
History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation in the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator

Sites / Locations

Cedars-Sinai Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Time-Restricted Eating (TRE)

Control

Arm Description

8-hour daily eating period, starting 1-3 hours after waking up

More than equal to a 12-hour daily eating period

Outcomes

Primary Outcome Measures

Treatment Related Toxicities

Will test to see if the toxicity index is different between the TRE and control groups as measured by the Common Terminology Criteria for Adverse Events (CTCAE). CTCAE includes all AEs and is graded as of 0 (absence of toxicity) to 5 (deceased), where 3 denotes a dose-limiting toxicity (DLT). This composite score accounts for the frequency and cumulative burden of all toxicities during the treatment period.

Patient-reported outcomes (PROs)

average and standard errors of patient-reported outcomes (PROs) as measured by the PRO-CTCAE which includes 78 treatment toxicities that patients can systematically document the frequency, severity (and interference of each toxicity). Descriptive statistics will be presented for both quantitative and qualitative variables, with profile plots showing the average and standard errors of PROs over time.

Secondary Outcome Measures

Signaling

IGF-1 and its binding proteins-IGFBP-1 and IGFBP-3-will be measured in serum collected in the morning after at least 8 hours of fasting. Descriptive statistics will be performed with IGF-1 and the ratios of IGF-1 to its two binding proteins as the response variables.

Mood

The NIH Patient-Reported Outcomes Measurement Information System (PROMIS®) was developed to standardize assessment of physical, mental, or social health patient-reported outcomes. Each questionnaire includes Likert-scale type questions ranging from 1-5. Total scores are converted to age-standardized T scores, for which normative mean is 50, and standard deviation is 10. The fatigue, pain, anxiety/depression, and physical function scales are validated in the cancer population. NIH PROMIS short forms will be used to assess symptoms of anxiety, depression. We will compare changes in PROMIS scores across study arms and test whether mood moderate relationships between intervention arms and clinical outcomes.

Psychosocial Functioning

Social Adjustment Scale-Self-Report (SAS-SR) assesses both behavioral and emotional social adjustment in the past two weeks across six domains: (1) paid or unpaid work, (2) social and leisure activities, (3) relationships with extended family, (4) role as a marital partner, (5) parental role, and (6) role within the family unit, including perceptions about economic functioning. Each area covers four expressive and instrumental categories: performance at expected tasks; the amount of friction with people; finer aspects of interpersonal relations; and feelings and satisfactions. Each question is rated on a five-point scale from which role area means, and an overall mean can be obtained, with higher scores denoting greater impairment. The instrument has good psychometric properties and is particularly well-tailored to assess whether work, family, and social functioning moderate the relationships between intervention arms and clinical outcomes.

Dietary Intake

will be assessed using interviewer-administered, multi-pass 24h-recalls. Participants will complete three in-person dietary recalls (two weekdays and one weekend day) at each assessment time point. The Nutrition Data System for Research software (NDSR; Nutrition Coordinating Center, University of Minnesota) will be used to analyze participants' dietary intake. We will assess changes in total energy (kcals), Healthy Eating Index (HEI 2015) as well as changes in added sugar, fruits, and vegetables, solid fats, alcoholic beverages, sodium, and fat. We will assess changes in dietary intake across study arms and examine whether these changes moderate the relationships between intervention arms and clinical outcomes.

Physical Activity

Physical activity will be operationalized as mean metabolic equivalent units (METs) per hour and percent of time spent in sedentary, light, moderate, and vigorous activity as assessed by Friedson (2011) algorithms.

Sleep

In accordance with recommendations for measuring sleep, Cole/Kripke scoring algorithms, will be used to determine the number of nighttime awakenings, sleep efficiency, and percent of time awake after sleep onset. The Pittsburgh sleep quality index (PSQI) will be used to assess subjective sleep quality and disturbance. The PSQI is one of the most commonly used self-rated questionnaires to assess sleep quality in clinical and nonclinical populations (5 minutes to complete). We will compare changes in physical activity and sleep (objective and subjective) across study arms and test whether the change in physical activity and sleep moderate the relationships between intervention arms and clinical outcomes.

Full Information

NCT ID

NCT04722341

First Posted

December 14, 2020

Last Updated

May 22, 2023

Sponsor

Cedars-Sinai Medical Center

Collaborators

National Cancer Institute (NCI), University of Alabama at Birmingham

1. Study Identification

Unique Protocol Identification Number

NCT04722341

Brief Title

Time-Restricted Eating and Cancer: Clinical Outcomes, Mechanisms, and Moderators

Official Title

Time-Restricted Eating and Cancer: Clinical Outcomes, Mechanisms, and Moderators

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 1, 2022 (Actual)

Primary Completion Date

June 30, 2026 (Anticipated)

Study Completion Date

December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Cedars-Sinai Medical Center

Collaborators

National Cancer Institute (NCI), University of Alabama at Birmingham

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

The purpose of this study is to test whether the timing of meals can improve treatment adverse events, influence tumor biology and alter a person's mood and behaviors.

Detailed Description

Combining fasting with chemotherapy is known to cause complete tumor regression and long-term survival in animal models. According to the Differential Stress Sensitization (DSS) theory, acute fasting sensitizes tumor cells to the cytotoxic effects of chemotherapy and radiation, while protecting healthy cells by increasing stress resistance. These effects are believed to be largely mediated via the Insulin-like Growth Factor (IGF-1) pathway. However, extended fasting can be challenging for patients and poses undue health risks. A number of alternative intermittent fasting regimens have been proposed to overcome the challenges of prolonged caloric restriction. One promising approach is time-restricted eating (TRE), which involves eating within a period of 10 hours or less, followed by fasting for at least 14 hours daily. TRE does not involve extended caloric restriction, and because of its simplicity, it may be more sustainable than other fasting regimens. TRE improves several cardiometabolic endpoints independent of calorie restriction in both animals and humans, including insulin sensitivity, blood pressure, fat oxidation, and hunger. Our team's pilot and feasibility trials suggest that TRE may also have anti-cancer effects: it decreases IGF-1 levels, reduces oxidative stress, upregulates antioxidant defenses, and enhances autophagy. Moreover, our data suggest TRE is sustainable, as participants were adherent 6.0 plus or minus 0.8 days/week over a 14-week period. These findings lead to the following provocative question: Can TRE reduce treatment-related toxicity, induce tumor regression, and improve both patient-reported and clinical outcomes? We propose to conduct the largest randomized controlled trial of any form of intermittent fasting in patients undergoing cancer treatment. We focus on patients with localized rectal cancer because it is one of the few treatment paradigms in which tumor characteristics can be measured before and after chemoradiation therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

Care ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Time-Restricted Eating (TRE)

Arm Type

Experimental

Arm Description

8-hour daily eating period, starting 1-3 hours after waking up

Arm Title

Control

Arm Type

Active Comparator

Arm Description

More than equal to a 12-hour daily eating period

Intervention Type

Behavioral

Intervention Name(s)

Time-Restricted Eating (TRE)

Intervention Description

8-hour daily eating period, starting 1-3 hours after waking up

Intervention Type

Behavioral

Intervention Name(s)

Control

Intervention Description

More than equal to a 12-hour daily eating period

Primary Outcome Measure Information:

Title

Treatment Related Toxicities

Description

Time Frame