Fiber-rich Foods to Treat Obesity and Prevent Colon Cancer

• ClinicalTrials.gov Identifier: NCT04780477
• Recruitment Status: Recruiting
• First Posted: March 3, 2021
• Last Update Posted: March 25, 2024
• Sponsor: Emory University
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Terry Hartman, Emory University

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Colon Cancer; Obesity	Dietary Supplement: High Fiber Diet Featuring Legumes (HLD); Dietary Supplement: Healthy American Diet	Not Applicable

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Fiber-rich Foods to Treat Obesity and Prevent Colon Cancer
• Actual Study Start Date: June 29, 2021
• Estimated Primary Completion Date: June 2025
• Estimated Study Completion Date: December 31, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: High Fiber Diet Featuring Legumes (HLD); Participants randomized to the high fiber diet featuring legumes (HLD) will add approximately 30 grams of dietary fiber per day from legume dishes, ensuring a total intake of approximately 50 grams of dietary fiber per day.	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.
Active Comparator: Healthy American Diet Control Arm; Participants randomized to the healthy American diet control arm will receive pre-portioned meal replacement entrées with legumes replaced by lean chicken or meat.	Dietary Supplement: 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.

Outcome Measures

Primary Outcome Measures :

1. Change in Body Weight [ Time Frame: Baseline, Month 6 (end of intense intervention) ]
   Participants will have their body weight measured (in pounds) on a regularly calibrated digital scale while wearing light clothing without shoes.
2. Change in Ki-67+ Level [ Time Frame: Baseline, Month 6 (end of intense intervention) ]
   Colonic mucosal proliferative biomarker Ki-67+ will be measured.

Secondary Outcome Measures :

1. Body Weight [ Time Frame: Month 12 ]
   Participants will have their body weight measured (in pounds) on a regularly calibrated digital scale while wearing light clothing without shoes.
2. Ki-67+ level [ Time Frame: Month 12 ]
   Colonic mucosal proliferative biomarker Ki-67+ will be measured
3. Change in Gut Transit Time [ Time Frame: Baseline, Month 6 (end of intense intervention) ]
   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.
4. Change in Fasting Plasma Insulin Level [ Time Frame: Baseline, Month 6, Month 12 ]
   Fasting plasma insulin, a biomarker of insulin resistance is measured by blood test.
5. Change in Fasting Plasma Glucose Level [ Time Frame: Baseline, Month 6, Month 12 ]
   Fasting plasma glucose, a biomarker of insulin resistance, is measured by blood test.
6. Change in Serum C-reactive Protein [ Time Frame: Baseline, Month 6, Month 12 ]
   Serum C-reactive protein, an indicator of systemic inflammation, is measured by blood test.
7. Change in CD3+ Intraepithelial Lymphocytes Count [ Time Frame: Baseline, Month 6, Month 12 ]
   CD3+ intraepithelial lymphocytes, a colonic mucosal inflammatory biomarker of colon cancer risk, will be measured by mucosal biopsy.
8. Change in CD68+ Lamina Propia Macrophages Count [ Time Frame: Baseline, Month 6, Month 12 ]
   CD68+ lamina propia macrophages, a colonic mucosal inflammatory biomarker of colon cancer risk, will be measured by mucosal biopsy.

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Terry Hartman, PhD, MPH, RD; 404-727-9134; tjhartm@emory.edu

Locations

United States, Georgia

Rollins School of Public Health, Emory University; Recruiting

Atlanta, Georgia, United States, 30322

Contact: Terry Hartman, PHD, MPH fiber.diet.study@emory.edu

Sponsors and Collaborators

Emory University

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Terry Hartman, PhD, MPH, RD; Emory University

More Information

• Responsible Party: Terry Hartman, Professor, Emory University
• ClinicalTrials.gov Identifier: NCT04780477
• Other Study ID Numbers: STUDY00000563; R01CA245063 ( U.S. NIH Grant/Contract )
• First Posted: March 3, 2021
• Last Update Posted: March 25, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified participant phenotypic data will be made available for sharing but limited to health/biomedical purposes including age, obesity status, presence of colon polyps and history of diabetes. The data will be coded and only the coded data set, and not the master list, will be shared.
• Supporting Materials: Study Protocol
• Time Frame: Individual participant data will be made available for sharing beginning 9 months and ending 36 months following publication of findings for this study.

Access Criteria

Proposals to share individual participant data should be directed to tjhartm@emory.edu. To gain access, requestors will need to sign a data access agreement.

To meet NIH data sharing requirements selected data will be deposited in appropriate research data repositories (e.g., NIH Common Fund Metabolomics Workbench). For genomic data, all data generated by this project will be made publicly available through adequate public genomic data warehouses as appropriate to the data type (NCBI Short Read Archives, Gene expression omnibus, etc.). Sequence data will be screened for the presence of sequences from human and these will be removed from public submissions unless directed otherwise by the NIH. Our algorithms will be made available through publications and as standalone programs when this is feasible. All new genomic and microbiome datasets will be deposited in public databases.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Terry Hartman, Emory University:

Fiber-rich Foods; Legumes; Weight loss; Intestinal health; Cancer prevention

Additional relevant MeSH terms:

Colonic Neoplasms; Obesity; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases