Diet Modulation of Bacterial Sulfur and Bile Acid Metabolism and Colon Cancer Risk

NCT03550885 | Enrolling By Invitation DMC

• 2 other identifiers: 2016-04951R01CA204808-01
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Determine in the context of a controlled crossover diet-intervention trial the role of taurocholic acid metabolism by gut bacteria in African American subjects at elevated risk for colorectal cancer (CRC). Two isocaloric diets, an animal-based diet high in taurine and saturated fat (HT-HSAT) and a plant-based, low in taurine and low saturated fat (LT-LSAT) will be used to determine the extent to which the relationship between diet (independent variable) and mucosal markers of CRC risk including epithelial proliferation, oxidative stress, DNA damage, and primary and secondary bile acid pools and biomarkers of inflammation (dependent variables) is explained by the abundance of sulfidogenic bacteria and hydrogen sulfide (H2S) concentrations \&/or deoxycholic acid (DCA) and DCA-producing bacteria clostridium scindens (mediator variables).

Conditions

Colorectal Cancer

Keywords

microbiome, human; bile acids and salts; diet, western

Outcome Measures

Primary Outcomes (1)

• Change in the mucosal abundance of bacterial genes associated with sulfur and bile acid metabolism

  Mucosal abundance of bacterial genes associated with sulfur and bile acid metabolism will be measured by quantitative polymerase chain reaction of 16S rRNA and functional genes with biopsy DNA.

  Baseline and post-diet (day 22) for each of the two 3-week diets

Secondary Outcomes (5)

• Change in bile acid metabolism

  Baseline and post-diet (day 22) for each of the two 3-week diets

• Change in serum bile acids

  Baseline and post-diet (day 22) for each of the two 3-week diets

• Change in colonic mucosal inflammation

  Baseline and post-diet (day 22) for each of the two 3-week diets

• Change in DNA damage

  Baseline and post-diet (day 22) for each of the two 3-week diets

• Change in colonocyte proliferation

  Baseline and post-diet (day 22) for each of the two 3-week diets

Study Arms (2)

High taurine and saturated fat diet

EXPERIMENTAL

This is a 3-week controlled isocaloric diet containing approximately 125 mg taurine, 40% of calories from fat, 15% of calories from saturated fat, 25% of calories from protein (4:1 animal to plant grams of protein), and 11.5 grams fiber/1000 calories.

Other: High taurine and saturated fat diet

Low in taurine and saturated fat diet

EXPERIMENTAL

This is a 3-week controlled isocaloric diet containing approximately 7 mg taurine, 36% of calories from fat, 8% of calories from saturated fat, 13% of calories from protein (3:1 plant to animal grams of protein), and 13.5 grams fiber/1000 calories.

Other: Low in taurine and saturated fat diet

Interventions

High taurine and saturated fat diet OTHER

This is a 3-week (21 day) isocaloric Western-type diet with all meals, snacks, beverages and condiments provided.

High taurine and saturated fat diet

Low in taurine and saturated fat diet OTHER

This is a 3-week (21 day) isocaloric largely plant-based diet with all meals, snacks, beverages and condiments provided.

Low in taurine and saturated fat diet

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult African American;
• Obese (defined as BMI 30 - \< 50 kg/m2);
• Age between 45 - 75 years old;
• Patients with an increased risk for CRC, defined as 3 or more adenomatous polyps or adenomatous polyp \> 1cm within 5-yrs of enrollment;
• An elevated C-reactive protein (CRP) (defined as \> 3 mg/l)
• Participants must be in good general health, not expecting major lifestyle changes in the next 6 months and willing to maintain their current activity level throughout the duration of the study.
• Women only: Post-menopausal (natural or surgical) defined as no menstruation in the past 6 months

You may not qualify if:

• BMI \< 30 or \> 50 kg/m2 (for those interested and eligible, verify BMI by measuring weight and height, complete the screening consent form before assessing these measures)
• Weight \> 450 lbs. (max weight for the body composition scanner)
• Race other than African American
• Women only: at least one menstrual period in the past 6 months
• Current malignancy except non-melanoma skin cancer that has been removed
• Current gastrointestinal (GI) illness other than gastroesophageal reflux disease or hemorrhoids (such as celiac disease, inflammatory bowel disease, malabsorptive bariatric procedures, etc.)
• Chronic liver or kidney disease (elevated liver tests \>3 times normal or creatinine above 2.0 mg/dl)
• History of cardiac disease (such as admission for congestive heart failure within the past 5 years, or being on anticoagulants for heart disease, or having an ejection fraction \<25%, etc.)
• Positive genetic test for inherited polyposis syndromes (such as familial adenomatous polyps, hereditary non-polyposis colon cancer syndromes, etc)
• Alcoholism or illicit drug use
• Antibiotic use within the past 2 months
• Regularly taking medications that may interfere with normal digestion (such as acarbose, cholestyramine, Orlistat, aspirin doses that exceed 81mg/day or 325 mg every other day)
• Anticoagulant use or other factors that increase endoscopic risks
• Non-English speaking
• Pregnant or breast feeding

Sponsors & Collaborators

• University of Illinois at Chicago: lead
• Rush University Medical Center: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Rush University Medical Center and University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Taurine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Lisa Tussing-Humphreys, PhD, MS, RD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

• Ece Mutlu, MD, MS, MBA

  Rush University Medical Center

  PRINCIPAL INVESTIGATOR

• H. Rex Gaskins, PhD

  University of Illinois at Urbana-Champaign

  PRINCIPAL INVESTIGATOR

• Jason Ridlon, PhD

  University of Illinois at Urbana-Champaign

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: All study personnel, excluding those directly involved with meal preparation, will be blinded to the subjects' diet sequence.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: The proposed study will utilize a randomized, crossover, controlled feeding trial design composed of two experimental diets: (1) animal-based, high in taurine and saturated fat (HT-HSAT) and (2) plant-based, low in both taurine and saturated fat (LT-LSAT) (each consumed for 21 days with a minimum 3-week washout between diets). At baseline and post-diet (day 22) for each of the two 3-week diets, subjects will undergo a flexible sigmoidoscopy, fasting and non-fasting blood draw, and provide a stool sample.

Study Record Dates

• First Submitted: May 24, 2018
• First Posted: June 8, 2018
• Study Start: August 1, 2018
• Primary Completion: December 15, 2025
• Study Completion: December 15, 2025
• Last Updated: August 13, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)