Fiber-rich Foods to Treat Obesity and Prevent Colon Cancer

Obesity Clinical Trial

Official title:

Fiber-rich Foods to Treat Obesity and Prevent Colon Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04780477
• Other study ID #: STUDY00000563
• Secondary ID: R01CA245063
• Status: Recruiting
• Phase: N/A
• Start date: June 29, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2024
• Source: Emory University
• Contact: Terry Hartman, PhD, MPH, RD
• Phone: 404-727-9134
• Email: tjhartm[@]emory.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study tests whether a high-fiber diet based on legumes, such as dry beans, can lead to sustained reductions in obesity and colon cancer risk in persons at highest risk, namely overweight or obese, post-polypectomy patients.

Description:

An important knowledge gap concerns the role of fiber in sustaining reduced energy intake to simultaneously manage weight and influence human colorectal cancer risk. Epidemiologic studies have shown an association between a high fiber diet featuring legumes (HLD) and reduced obesity and lower risk for adenoma recurrence or colorectal cancer. There are many plausible mechanisms to explain why high-fiber diets, and especially a HLD, may reduce colorectal cancer risk. First, fiber is fermented by the colonic microbiota to produce short chain fatty acids (SCFA). The SCFA, butyrate, has a remarkable array of colonic mucosal health promoting, anti-inflammatory, and anti-neoplastic properties. Secondly, microbiota break down plant cell walls releasing phytochemicals, which also have powerful anti-inflammatory and anti-carcinogenic effects. Thirdly, colonic transit is accelerated, reducing contact time with luminal carcinogens, such as heterocyclic amines formed from cooked red meat, and secondary bile acids, induced by a high fat diet and synthesized by the colonic microbiota. Dr. Stephen O'Keefe's lab performed a human randomized controlled crossover feeding study (participants receive both diets) comparing high and low- fiber diets. The study measured mucosal biomarkers of cancer risk (proliferation - % epithelial cells staining positive for Ki67, inflammation - cluster of differentiation 3 (CD3)+ intraepithelial lymphocytes, cluster of differentiation 68 (CD68)+ lamina propria macrophages) made by fecal sampling and colonoscopy. Results suggested that within weeks these markers responded favorably to the high-fiber diet with proliferative rates and inflammatory biomarkers decreasing and microbiota composition adapting to increase butyrogenesis. The researchers of this study have previously found that fiber may also reduce cancer risk indirectly by promoting weight loss, improving insulin sensitivity and decreasing inflammation. On average, individuals consume a similar weight of food daily; thus, replacing energy dense foods (higher kcal/g, e.g., high fat) with lower energy density foods (lower kcal/g), like legumes, should potentiate weight control. Viscous fiber intake is associated with longer gastric emptying times which over time might contribute to postponing the next eating occasion. Diet may also induce changes in gut microbiome composition leading to negative energy balance. Emerging human evidence links the gut microbiome with insulin resistance, inflammation, and obesity and with adenomatous polyps and colon cancer. In this current study, characterizing gut motility, microbiome, and metabolome composition profiles that may influence weight loss and have a role in the prevention or recurrence of adenomas and colorectal cancer, will provide novel and potentially therapeutic information. The goal of the research is to conduct a clinical trial featuring study-provided pre-portioned entrées and strategic nutritional instruction to guide participants to integrate legumes into a healthy high-fiber diet pattern. Participants will be provided two entrées per day during months 1 through 3, and one entrée per day during months 4 through 6. Participants will continue their diets during months 7 through 12 but will be responsible for food preparation. The research will target a population at high risk for colorectal cancer, overweight and obese participants with a history of a colon polyp in the past 3 years, to test whether a high-legume, high-fiber diet will simultaneously increase weight loss and suppress intestinal biomarkers of cancer risk compared to a control diet (healthy American). In addition, it will explore potential mechanisms through which the high-legume intervention diet facilitates weight loss and intestinal health.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: December 31, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

• free-living adults 40 to 75 years old
• BMI 25-40 kg/m^2
• able to provide documentation confirming a colonoscopy within 3 years that found =1 adenoma >0.5 cm or a sessile serrated polyp (any)
• English speaking
• ambulatory, able to pick up food, participate in clinical exams and laboratory tests
• able to provide informed consent

Exclusion Criteria:

• serious and/or unstable medical condition as deemed by study physician
• history of colorectal cancer, bowel resection, polyposis syndrome, or inflammatory bowel disease
• smoked regularly in the past year
• dietary restrictions substantially limiting compliance (e.g., must be willing to be randomized to either diet)
• planning on substantially changing usual exercise behavior in the next 6 months
• regular or recent use of prescription medication that may alter inflammation markers or gut function as deemed by study physician
• pregnant women, breast feeding women, or women planning pregnancy within the year of active study participation

Related Conditions & MeSH terms

• Colon Cancer
• Colonic Neoplasms
• Obesity

Intervention

Dietary Supplement:
• High Fiber Diet Featuring Legumes (HLD)
The high fiber diet featuring legumes (HLD) provides pre-portioned entrées for two meals per day in months 1-3, and one meal per day in months 4-6. Participants continue on the diet in months 7-12 but assume responsibility for food preparation. The HLD will contain approximately 250 grams (g) of legumes per day (~1 ½ cups cooked legumes) in months 1-3 provided in two pre-portioned single serving entrées (i.e. ~125g in each serving). A study nutritionist provides in-person and written guidance for including side dishes that are nutritionally balanced with energy intake to lose 1-2 pounds of weight per week.
• Healthy American Diet
The healthy American diet provides pre-portioned meal replacement entrées with legumes replaced by lean chicken or meat. Participants continue on the diet in months 7-12 but assume responsibility for food preparation. A study nutritionist provides in-person and written guidance for including side dishes that are nutritionally balanced with energy intake to lose 1-2 pounds of weight per week.

Locations

Country	Name	City	State
United States	Rollins School of Public Health, Emory University	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Body Weight	Participants will have their body weight measured (in pounds) on a regularly calibrated digital scale while wearing light clothing without shoes.	Baseline, Month 6 (end of intense intervention)
Primary	Change in Ki-67+ Level	Colonic mucosal proliferative biomarker Ki-67+ will be measured.	Baseline, Month 6 (end of intense intervention)
Secondary	Body Weight	Participants will have their body weight measured (in pounds) on a regularly calibrated digital scale while wearing light clothing without shoes.	Month 12
Secondary	Ki-67+ level	Colonic mucosal proliferative biomarker Ki-67+ will be measured	Month 12
Secondary	Change in Gut Transit Time	Gut transit time is assessed using an indigestible single-use SmartPill capsule, a receiver, and display software. The SmartPill capsules were discontinued and no longer available after 2023 so participants beginning after January 19, 2024 will not complete this assessment.	Baseline, Month 6 (end of intense intervention)
Secondary	Change in Fasting Plasma Insulin Level	Fasting plasma insulin, a biomarker of insulin resistance is measured by blood test.	Baseline, Month 6, Month 12
Secondary	Change in Fasting Plasma Glucose Level	Fasting plasma glucose, a biomarker of insulin resistance, is measured by blood test.	Baseline, Month 6, Month 12
Secondary	Change in Serum C-reactive Protein	Serum C-reactive protein, an indicator of systemic inflammation, is measured by blood test.	Baseline, Month 6, Month 12
Secondary	Change in CD3+ Intraepithelial Lymphocytes Count	CD3+ intraepithelial lymphocytes, a colonic mucosal inflammatory biomarker of colon cancer risk, will be measured by mucosal biopsy.	Baseline, Month 6, Month 12
Secondary	Change in CD68+ Lamina Propia Macrophages Count	CD68+ lamina propia macrophages, a colonic mucosal inflammatory biomarker of colon cancer risk, will be measured by mucosal biopsy.	Baseline, Month 6, Month 12