Time-restricted Eating Versus Daily Continuous Calorie Restriction on Body Weight and Colorectal Cancer Risk Markers

Effects of Time-restricted Eating Versus Daily Continuous Calorie Restriction on Body Weight and Colorectal Cancer Risk Markers Among Adults With Obesity

Approximately 42% of American adults are obese, and this condition is strongly related to the development of colorectal cancer. Innovative lifestyle strategies to treat obesity and reduce colorectal cancer risk are critically needed. This research will demonstrate that time-restricted eating, a type of intermittent fasting, is an effective therapy to help obese individuals reduce and control their body weight and prevent the development of colorectal cancer.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Colorectal Cancer; Weight Loss; Time Restricted Eating
• Intervention / Treatment: Behavioral: Time restricted eating; Behavioral: Calorie Restriction

Detailed Description

Approximately 42% of the U.S. adult population is obese and data suggests that persons with obesity are at a 30% greater risk of developing colorectal cancer (CRC). Therefore, efficacious approaches to preventing and treating obesity will have significant effects on CRC incidence in the U.S. Although calorie restriction through lifestyle intervention is the most common approach to treat obesity, clinically meaningful weight loss is difficult to achieve via this method due to low adherence with calorie monitoring, indicating a need for innovation. Time-restricted eating, a type of intermittent fasting, has been shown in animals to impart cancer protective effects including lower body weight, decreased systemic inflammation, and improved glucose metabolism. Time-restricted eating is where individuals are asked to consume all their food for the day within a specified time frame, and water fast for the remaining hours of the day. We recently performed two short-term (≤12-weeks) pilot studies of time-restricted eating to evaluate its safety and preliminary efficacy on body weight and chronic disease risk markers in adults with obesity. Our results show the intervention is a safe and acceptable approach to weight loss among obese adults. Moreover, time-restricted eating produced approximately 3% weight loss from baseline and reductions in systolic blood pressure, oxidative stress and insulin resistance. Although these pilot findings show promise for time-restricted eating as an effective tool for CRC risk reduction among obese individuals, these data still require confirmation by a well powered longer-term clinical trial. The present proposal aims to implement a 12-month (6-month intervention, 6-month maintenance) controlled, parallel arm trial among 255 obese adults (45-70 years old) who have had a colonoscopy. Subjects will be randomized to 1 of 3 groups: 1) 8-hour time-restricted eating (daily ad libitum food intake from 12pm - 8pm), 2) Calorie restriction (daily 25% calorie restriction), or 3) Control (daily ad libitum food intake, no meal timing restrictions) to compare the effects on: (1) Body weight, body composition, and intervention adherence; (2) Circulating metabolic, inflammation, and oxidative stress-related biomarkers; (3) Colonic mucosal gene expression profiles and mucosal inflammation, DNA damage and cellular growth; and (4) maintenance of benefits on body weight/composition and CRC markers.

• Study Type: Interventional
• Enrollment (Estimated): 255
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lisa Tussing-Humphreys, PhD, MS, RD; Phone Number: 312-355-5521; Email: ltussing@uic.edu
• Study Contact Backup: Name: Krista Varady, PhD; Phone Number: 312-996-7897; Email: varady@uic.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • University of Illinois at Chicago
      • Contact: Lisa Tussing-Humphreys; Phone Number: 312-355-5521; Email: ltussing@uic.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. 45-70 years old,
2. BMI 30-49.99 kg/m2
3. Are up to date with CRC screening.

Exclusion Criteria:

1. Have a history of renal disease, autoimmune disorders, immunodeficiency, malabsorptive disorder, significant gastrointestinal and hepatic disease, surgical change in gastrointestinal anatomy, severe ischemic heart disease, severe pulmonary disease, severe mental health disorder, eating disorder, or bariatric surgery;
2. Abuse alcohol (> 50 grams/day), illicit drugs (other than self-reported marijuana use), or use combustible tobacco;
3. Have controlled type 2 diabetes or undiagnosed uncontrolled diabetes based on hemoglobin A1c (HbA1c) > 9.0%;
4. Have a history of cancer treatment within the past 12 months, CRC, genetic predisposition to CRC (e.g., Lynch syndrome);
5. Have a baseline body weight > 450 lbs (weight limitation of the DXA);
6. Are on a weight loss diet or actively involved in a formal weight loss program (e.g., Weight Watchers);
7. Are not weight stable for 3 months prior to the study (weight gain or loss > 4 kg);
8. Are unable to keep a food diary for 7 consecutive days during screening;
9. Are night shift workers;
10. Are pregnant or trying to get pregnant;
11. Are taking drugs that influence study outcomes (weight loss medications);
12. Are non-English speaking
13. Are taking anticoagulant medications or medications with endoscopic risk
14. Are taking antivirals or immunosuppressant medications
15. Don't have regular access to an email address and computer/smartphone/tablet
16. Are currently following a diet that requires fasting on a weekly basis
17. Currently eat for less than 10 hours of the day (determined by asking participants what time they start and stop eating on a usual day)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Time Restricted Eating (TRE); During the active weight loss period, the TRE group will be instructed to eat ad libitum from 12:00pm - 8:00pm daily and fast from 8:00pm - 12:00pm. During the 8-h eating window, there will be no restrictions on types or quantities of foods consumed. During the fasting period, participants will be encouraged to drink plenty of water and may consume energy-free beverages, such as black tea or coffee. TRE subjects will meet with the TRE dietitian for 30 minutes at the start of the intervention to review instructions and goals, and then every week throughout the active weight loss period to review intervention adherence. At the beginning of the maintenance phase, total energy needs will be reassessed. Subjects will be instructed to main their body weight by consuming meals in an extended 10-h eating window every day and water fast between 8pm and 10 am, respectively.	Behavioral: Time restricted eating; daily ad libitum food intake, 8-h 12pm - 8pm, 6 m active weight loss phase; 10-h 10am-8pm, 6 m maintenance phase
Active Comparator: Calorie Restriction (Cal-R); Cal-R subjects will be instructed to restrict energy intake by 25% of their baseline total energy expenditure (TEE) daily. Subjects will meet with a study dietitian for a 60-min one-on-one session to develop individualized weight loss meal plans to help them adhere to their calorie restriction goal. Meal plans will include portion sizes and food lists that are consistent with their food preferences and prescribed calorie levels for weight loss. Food scales will be provided to help with food portioning. Cal-R subjects will meet with the dietitian every week throughout the weight loss period to review intervention adherence and modify the meal plans as needed. Subjects will be asked to maintain their baseline level of physical activity. At the beginning of the weight maintenance phase, total energy needs will be reassessed.	Behavioral: Calorie Restriction; daily 25% calorie restriction, 6 m active weight loss phase; 100% energy needs, 6 m maintenance phase
No Intervention: Control; Controls will be instructed to maintain their weight throughout the 12 m trial and to not change eating or physical activity habits. Controls will not receive dietary counseling. Controls will visit the research center every 3 months for outcome measurements.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight change (% kg)	Body weight in kg	Baseline to month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total and regional body fat composition and distribution	Total and regional body fat composition and distribution will be measured via whole body DEXA scan	Baseline, 6 month and 12 month
Intervention adherence	Measured through electronic diet records and 24 hour dietary recalls	Monthly, through month 6
Colonic mucosa gene expression profiling	Commercially available targeted transcriptomics platform	Baseline, month 6, month 12
Ki-67, proliferation	Healthy colonic mucosa, immunohistochemistry	Baseline, month 6, month 12
c-caspase-3, Bax, apoptosis	Healthy colonic mucosa, immunohistochemistry,	Baseline, month 6, month 12
CD3, CD163, pIKKa/b, tissue markers of inflammation	Healthy colonic mucosa, immunohistochemistry	Baseline, month 6, month 12
Weight maintenance (% kg)	Maintenance of weight loss	Month 6 to month 12
Fasting plasma glucose	From fasting venous blood measured by a commercial lab	Baseline, month 3, month 6, month 9, month 12
Plasma cytokines TNF-α, IL-6, IL1-β, and IL-10, %	Multiplex ELISA	Baseline, month 3, month 6, month 9, month 12
Plasma 8-isoprostane	ELISA	Baseline, month 3, month 6, month 9, month 12
Fasting plasma insulin	From fasting venous blood measured at a commercial lab	Baseline, month 3, month 6, month 9, month 12
HOMA-IR	calculated from fasting glucose and insulin using a standard formula	Baseline, month 3, month 6, month 9, month 12
Gut Microbiome	Shotgun metagenomics	Baseline, month 3 and month 6
Fecal Metabolites	Untargeted Metabolomics	Baseline, month 3 and month 6
Saliva microbiota	Untargeted Metabolomics	Baseline, month 3, month 6

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Lisa Tussing-Humphreys, PhD, MS, RD, University of Illinois at Chicago

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: September 29, 2021
• First Submitted That Met QC Criteria: November 5, 2021
• First Posted (Actual): November 10, 2021

Study Record Updates

• Last Update Posted (Actual): May 9, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Overnutrition; Nutrition Disorders; Overweight; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Body Weight Changes; Obesity; Colorectal Neoplasms; Weight Loss; Body Weight
• Other Study ID Numbers: 2020-1627; 1R01CA257807 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No