- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04780477
Fiber-rich Foods to Treat Obesity and Prevent Colon Cancer
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Terry Hartman, PhD, MPH, RD
- Phone Number: 404-727-9134
- Email: tjhartm@emory.edu
Study Locations
-
-
Georgia
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Atlanta, Georgia, United States, 30322
- Recruiting
- Rollins School of Public Health, Emory University
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Contact:
- Terry Hartman, PHD, MPH
- Email: fiber.diet.study@emory.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / 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.
|
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.
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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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Body Weight
Time Frame: Baseline, Month 6 (end of intense intervention)
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Participants will have their body weight measured (in pounds) on a regularly calibrated digital scale while wearing light clothing without shoes.
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Baseline, Month 6 (end of intense intervention)
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Change in Ki-67+ Level
Time Frame: Baseline, Month 6 (end of intense intervention)
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Colonic mucosal proliferative biomarker Ki-67+ will be measured.
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Baseline, Month 6 (end of intense intervention)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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Month 12
|
Ki-67+ level
Time Frame: Month 12
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Colonic mucosal proliferative biomarker Ki-67+ will be measured
|
Month 12
|
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.
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Baseline, Month 6 (end of intense intervention)
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Change in Fasting Plasma Insulin Level
Time Frame: Baseline, Month 6, Month 12
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Fasting plasma insulin, a biomarker of insulin resistance is measured by blood test.
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Baseline, Month 6, Month 12
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Change in Fasting Plasma Glucose Level
Time Frame: Baseline, Month 6, Month 12
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Fasting plasma glucose, a biomarker of insulin resistance, is measured by blood test.
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Baseline, Month 6, Month 12
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Change in Serum C-reactive Protein
Time Frame: Baseline, Month 6, Month 12
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Serum C-reactive protein, an indicator of systemic inflammation, is measured by blood test.
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Baseline, Month 6, Month 12
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Change in CD3+ Intraepithelial Lymphocytes Count
Time Frame: Baseline, Month 6, Month 12
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CD3+ intraepithelial lymphocytes, a colonic mucosal inflammatory biomarker of colon cancer risk, will be measured by mucosal biopsy.
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Baseline, Month 6, Month 12
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Change in CD68+ Lamina Propia Macrophages Count
Time Frame: Baseline, Month 6, Month 12
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CD68+ lamina propia macrophages, a colonic mucosal inflammatory biomarker of colon cancer risk, will be measured by mucosal biopsy.
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Baseline, Month 6, Month 12
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Terry Hartman, PhD, MPH, RD, Emory University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- STUDY00000563
- R01CA245063 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing 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.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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