Clinical trial NCT05114798: Time-restricted Eating Versus Daily Continuous Calorie Restriction on Body Weight and Colorectal Cancer Risk Markers
Official title: Effects of Time-restricted Eating Versus Daily Continuous Calorie Restriction on Body Weight and Colorectal Cancer Risk Markers Among Adults With Obesity
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Time Restricted Eating
Obesity
Weight Loss
Colorectal Cancer
Lead sponsor: University of Illinois at Chicago
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2021-11-10
Enrollment: 255
Sex: ALL
Minimum age (years): 45
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized by the data manager, by way of a stratified random sample in 1:1:1 ratio. The sample frame will be divided into strata based on BMI, sex, and age. Subjects from each stratum, will then be randomized to 1 of 3 groups: 1) TRE, 2) Cal-R, or 3) Control.
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Weight change (% kg)
timeFrame: Baseline to month 6
Secondary outcomes:
measure: Total and regional body fat composition and distribution
timeFrame: Baseline, 6 month and 12 month
measure: Intervention adherence
timeFrame: Monthly, through month 6
measure: Fasting plasma glucose
timeFrame: Baseline, month 3, month 6, month 9, month 12
measure: Plasma cytokines TNF-α, IL-6, IL1-β, and IL-10, %
timeFrame: Baseline, month 3, month 6, month 9, month 12
measure: Plasma 8-isoprostane
timeFrame: Baseline, month 3, month 6, month 9, month 12
measure: Colonic mucosa gene expression profiling
timeFrame: Baseline, month 6, month 12
measure: Ki-67, proliferation
timeFrame: Baseline, month 6, month 12
measure: c-caspase-3, Bax, apoptosis
timeFrame: Baseline, month 6, month 12
measure: CD3, CD163, pIKKa/b, tissue markers of inflammation
timeFrame: Baseline, month 6, month 12
measure: Weight maintenance (% kg)
timeFrame: Month 6 to month 12
measure: Fasting plasma insulin
timeFrame: Baseline, month 3, month 6, month 9, month 12
measure: HOMA-IR
timeFrame: Baseline, month 3, month 6, month 9, month 12
measure: Gut Microbiome
timeFrame: Baseline, month 3 and month 6
measure: Fecal Metabolites
timeFrame: Baseline, month 3 and month 6
measure: Saliva microbiota
timeFrame: Baseline, month 3, month 6
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
Study officials:
affiliation: University of Illinois at Chicago
name: Lisa Tussing-Humphreys, PhD, MS, RD
role: PRINCIPAL_INVESTIGATOR
References: