Colorectal Cancer, Obesity, Time Restricted Eating, Weight Loss
Conditions
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.
Interventions
BEHAVIORALTime 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
BEHAVIORALCalorie Restriction
daily 25% calorie restriction, 6 m active weight loss phase; 100% energy needs, 6 m maintenance phase
Sponsors
University of Illinois at Chicago
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
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.
Eligibility
Sex/Gender
ALL
Age
45 Years to 70 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weight change (% kg) | Baseline to month 6 | Body weight in kg |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total and regional body fat composition and distribution | Baseline, 6 month and 12 month | Total and regional body fat composition and distribution will be measured via whole body DEXA scan |
| Intervention adherence | Monthly, through month 6 | Measured through electronic diet records and 24 hour dietary recalls |
| Fasting serum glucose | Baseline, month 3, month 6, month 9, month 12 | From fasting venous blood measured by a commercial lab |
| Plasma cytokines TNF-α, IL-6, IL1-β, and IL-10, % | Baseline, month 3, month 6, month 9, month 12 | Multiplex ELISA |
| Plasma 8-isoprostane | Baseline, month 3, month 6, month 9, month 12 | ELISA |
| Colonic mucosa gene expression profiling | Baseline, month 6, month 12 | Commercially available targeted transcriptomics platform |
| Ki-67, proliferation | Baseline, month 6, month 12 | Healthy colonic mucosa, immunohistochemistry |
| c-caspase-3, Bax, apoptosis | Baseline, month 6, month 12 | Healthy colonic mucosa, immunohistochemistry, |
| CD3, CD163, pIKKa/b, tissue markers of inflammation | Baseline, month 6, month 12 | Healthy colonic mucosa, immunohistochemistry |
| Weight maintenance (% kg) | Month 6 to month 12 | Maintenance of weight loss |
| Fasting serum insulin | Baseline, month 3, month 6, month 9, month 12 | From fasting venous blood measured at a commercial lab |
| HOMA-IR | Baseline, month 3, month 6, month 9, month 12 | calculated from fasting glucose and insulin using a standard formula |
| Gut Microbiome | Baseline, month 3 and month 6 | Shotgun metagenomics |
| Fecal Metabolites | Baseline, month 3 and month 6 | Untargeted Metabolomics |
| Saliva microbiota | Baseline, month 3, month 6 | Untargeted Metabolomics |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORLisa Tussing-Humphreys, PhD, MS, RD
University of Illinois at Chicago
Outcome results
None listed