Clinical trial NCT04780477: Fiber-rich Foods to Treat Obesity and Prevent Colon Cancer
Official title: Fiber-rich Foods to Treat Obesity and Prevent Colon Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Colon Cancer
Obesity
Keywords: Fiber-rich Foods
Legumes
Weight loss
Intestinal health
Cancer prevention
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2021-03-03
Enrollment: 60
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility 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

Primary outcomes:
measure: Change in Body Weight
timeFrame: Baseline, Month 6 (end of intense intervention)
measure: Change in Ki-67+ Level
timeFrame: Baseline, Month 6 (end of intense intervention)
Secondary outcomes:
measure: Body Weight
timeFrame: Month 12
measure: Ki-67+ level
timeFrame: Month 12
measure: Change in Gut Transit Time
timeFrame: Baseline, Month 6 (end of intense intervention)
measure: Change in Fasting Plasma Insulin Level
timeFrame: Baseline, Month 6, Month 12
measure: Change in Fasting Plasma Glucose Level
timeFrame: Baseline, Month 6, Month 12
measure: Change in Serum C-reactive Protein
timeFrame: Baseline, Month 6, Month 12
measure: Change in CD3+ Intraepithelial Lymphocytes Count
timeFrame: Baseline, Month 6, Month 12
measure: Change in CD68+ Lamina Propia Macrophages Count
timeFrame: Baseline, Month 6, Month 12
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Rollins School of Public Health, Emory University
state: Georgia
Study officials:
affiliation: Emory University
name: Terry Hartman, PhD, MPH, RD
role: PRINCIPAL_INVESTIGATOR
References: