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

• ClinicalTrials.gov Identifier: NCT04722341
• Recruitment Status: Recruiting
• First Posted: January 25, 2021
• Last Update Posted: April 27, 2022
• Sponsor: Cedars-Sinai Medical Center
• Collaborators: National Cancer Institute (NCI); University of Alabama at Birmingham
• Information provided by (Responsible Party): Sarah Salvy, Cedars-Sinai Medical Center

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.

Condition or disease	Intervention/treatment	Phase
Colo-rectal Cancer	Behavioral: Time-Restricted Eating (TRE); Behavioral: Control	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Time-Restricted Eating and Cancer: Clinical Outcomes, Mechanisms, and Moderators
• Actual Study Start Date: January 1, 2022
• Estimated Primary Completion Date: December 2026
• Estimated Study Completion Date: December 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Time-Restricted Eating (TRE); 8-hour daily eating period, starting 1-3 hours after waking up	Behavioral: Time-Restricted Eating (TRE); 8-hour daily eating period, starting 1-3 hours after waking up
Active Comparator: Control; More than equal to a 12-hour daily eating period	Behavioral: Control; More than equal to a 12-hour daily eating period

Outcome Measures

Primary Outcome Measures :

1. Treatment Related Toxicities [ Time Frame: at end of 6 month intervention ]
   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.
2. Patient-reported outcomes (PROs) [ Time Frame: at end of 6 month intervention ]
   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 :

1. Signaling [ Time Frame: at end of 6 month intervention ]
   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.
2. Mood [ Time Frame: at end of 6 month intervention ]
   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.
3. Psychosocial Functioning [ Time Frame: at end of 6 month intervention ]
   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.
4. Dietary Intake [ Time Frame: at end of 6 month intervention ]
   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.
5. Physical Activity [ Time Frame: at end of 6 month intervention ]
   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.
6. Sleep [ Time Frame: at end of 6 month intervention ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 21 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Nathalie Nguyen, MPH; 310.423.4209; nathalie.nguyen@cshs.org

Locations

United States, California

Cedars-Sinai Medical Center; Recruiting

West Hollywood, California, United States, 90048

Contact: Nathalie Nguyen, MPH

Sponsors and Collaborators

Cedars-Sinai Medical Center

National Cancer Institute (NCI)

University of Alabama at Birmingham

More Information

• Responsible Party: Sarah Salvy, Professor, Cedars-Sinai Medical Center
• ClinicalTrials.gov Identifier: NCT04722341
• Other Study ID Numbers: 15494
• First Posted: January 25, 2021
• Last Update Posted: April 27, 2022
• Last Verified: April 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases