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
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
Eligibility 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
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
No
Studies a U.S. FDA-regulated Device Product
No
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
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.
Time Frame
at end of 6 month intervention
Title
Patient-reported outcomes (PROs)
Description
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.
Time Frame
at end of 6 month intervention
Secondary Outcome Measure Information:
Title
Signaling
Description
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.
Time Frame
at end of 6 month intervention
Title
Mood
Description
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.
Time Frame
at end of 6 month intervention
Title
Psychosocial Functioning
Description
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.
Time Frame
at end of 6 month intervention
Title
Dietary Intake
Description
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.
Time Frame
at end of 6 month intervention
Title
Physical Activity
Description
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.
Time Frame
at end of 6 month intervention
Title
Sleep
Description
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.
Time Frame
at end of 6 month intervention
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Any sex/gender of any ethnic/racial background
Age greater than or equal to 18 years
Histologically confirmed rectal cancer stage II, III, or IV (if curative) per AJCC criteria
BMI 18.5 kg/m2 or greater
Will receive total neoadjuvant therapy (TNT) with 5-FU based regimens
Willing and able to adhere to the assessments, visit schedules, prohibitions, and restrictions
Exclusion Criteria:
History of cytotoxic chemotherapy less than or equal to 12 months prior to rectal cancer diagnosis
Allergic reaction to any of the treatment agents
Any prior pelvic radiotherapy
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 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
Pregnant or breastfeeding
Currently perform overnight shift work more than one day/week on average
Strictly adhering to a <10-hour eating window on most days
Known psychiatric or substance abuse disorders that would interfere with adhering to the requirements of the trial
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nathalie Nguyen, MPH
Phone
310.423.4209
Email
nathalie.nguyen@cshs.org
Facility Information:
Facility Name
Cedars-Sinai Medical Center
City
West Hollywood
State/Province
California
ZIP/Postal Code
90048
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nathalie Nguyen, MPH
12. IPD Sharing Statement
Learn more about this trial
Time-Restricted Eating and Cancer: Clinical Outcomes, Mechanisms, and Moderators
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