Mediterranean Diet and Weight Loss: Targeting the Bile Acid/Gut Microbiome Axis to Reduce Colorectal Cancer

NCT ID: NCT04753359

Last Updated: 2024-08-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 232 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-01
• Study Completion Date: 2025-03-31

Brief Summary

A Mediterranean Diet (MedDiet), a largely plant-based dietary pattern, is relevant to CRC prevention and microbial production of anti-cancer metabolites in observational studies. A MedDiet can shift BA metabolism as shown in primates and when combined with calorie restriction, shows superior adherence and weight control in humans, given its palatability. To date, no studies have tested in an RCT the effects of a MedDiet alone (MedA), WL through lifestyle intervention (WL-A) or a calorie-restricted MedDiet for WL (WL-Med) on the BA-gut microbiome axis and its relevance to CRC prevention among AAs. A multidisciplinary team combining expertise in psychology, nutrition, microbiology, molecular cell biology, computational biology, medicine and biostatistics, proposes to conduct a four-arm RCT in which 232 obese AAs, 45-75 years old complete one of the following 6-month interventions: Med-A, weight stable; WL-A, calorie restriction with no diet pattern change; WLMed; or Control. The investigators will use samples and data collected at baseline, mid-study (month-3) and post-intervention to compare the effects of the interventions on 1) Concentration and composition of circulating and fecal BAs; 2) Gut microbiota and metabolic function; and 3) Gene expression profiles of exfoliated intestinal epithelial cells.

Detailed Description

Colorectal cancer (CRC) is associated with multiple risk factors including, obesity, low fiber diets, and diets high in animal protein and saturated fat (SFat). African Americans (AAs) have a higher prevalence of these risk factors and they have the highest incidence of CRC and related mortality. These multiple risk factors are also linked to higher circulating and fecal bile acids (BA) and a shift in BA amino acid conjugation from glycine to taurine. These BA-related changes can alter the composition, structure, and metabolic activity of the gut microbiota, fostering conditions for gut bacteria to expand and metabolize taurine-conjugated BAs to genotoxic hydrogen sulfide (H2S) and the tumor promoter, deoxycholic acid (DCA); a colonic milieu conducive to the formation of CRC. The investigators have shown that the abundance of H2S-producing bacteria is significantly higher in the colon of AAs compared to non-Hispanic whites (NHWs) and is a defining feature among AA CRC cases implicating these bacteria as contributors to CRC development in a race-dependent manner. Moreover, the microbial difference is associated with higher intake of SFat and animal protein in AAs, providing a pivotal intervention target. The investigators hypothesize that targeting the BA-gut microbiome axis to suppress abundance, growth and metabolic activity of H2S and DCA producing bacteria through diet and weight loss (WL) may reduce CRC risk, especially among AAs. A Mediterranean Diet (MedDiet), a largely plant-based dietary pattern, is relevant to CRC prevention and microbial production of anti-cancer metabolites in observational studies. A MedDiet can shift BA metabolism as shown in primates and when combined with calorie restriction, shows superior adherence and weight control in humans, given its palatability. To date, no studies have tested in an RCT the effects of a MedDiet alone (MedA), WL through lifestyle intervention (WL-A) or a calorie-restricted MedDiet for WL (WL-Med) on the BA-gut microbiome axis and its relevance to CRC prevention among AAs. Our multidisciplinary team combining expertise in psychology, nutrition, microbiology, molecular cell biology, computational biology, medicine and biostatistics, propose to conduct a four-arm RCT in which 232 obese AAs, 45-75 years old complete one of the following 6-month interventions: Med-A, weight stable; WL-A, calorie restriction with no diet pattern change; WLMed; or Control. The investigators will use samples and data collected at baseline, mid-study (month-3) and post-intervention to compare the effects of the interventions on 1) Concentration and composition of circulating and fecal BAs; 2) Gut microbiota and metabolic function; and 3) Gene expression profiles of exfoliated intestinal epithelial cells. The investigators approach is strong given the multidisciplinary team, use of evidence-based lifestyle interventions, and sophisticated -omics analyses to examine crosstalk between diet/WL, gut microbiome, and host intestinal physiology. If successful, this study could have profound public health impact on CRC risk among AAs and other high-risk populations, that would translate into timely dissemination opportunities.

Conditions

Colorectal Cancer; Diet Habit

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Med-A

Med-A will attend a one-hour, in-person individual session with a registered dietitian (RD) during the two weeks prior to the start of the intervention. For subjects randomized to Med-A the study RD will instruct on adoption of an eating pattern consistent with a MedDiet using an individualized MedDiet exchange list and companion guide. Recommended daily exchanges are based on individual caloric needs to maintain weight. We will not ask subjects to abstain from alcohol during the trial despite its known effects on BA metabolism, but we will recommend that only 5% of calories come from alcohol taken with meals. Following the initial session, subjects will meet for 24 individual sessions (1-hour, held approximately weekly) in-person or virtually over the remaining 6 months. Additional asynchronous learning materials will be distributed weekly through a private Facebook group.

The Med-A group will be asked to maintain their usual physical activity.

Group Type: EXPERIMENTAL

Med

Intervention Type: OTHER

Mediterranean diet

WL-A

WL-A will attend a one-hour, in-person individual session with a registered dietitian (RD) during the two weeks prior to the intervention. For WL-A, the focus will be on daily calorie restriction (-500-750 kcal/day) to achieve a 1-2 lb. per week WL and 5% WL from baseline at 6 months in the context of the subject's typical diet pattern. We will not ask subjects to abstain from alcohol during the trial despite its known effects on BA metabolism, but we will recommend that only 5% of calories come from alcohol taken with meals. Following the initial session, subjects will meet for 24 individual, virtual or in-person sessions (1-hour, held approximately weekly) over the remaining 6 months. Additional asynchronous learning materials will be distributed weekly through a private Facebook group.

The WL-A group will be prescribed an activity program. Physical activity will be monitored via FitBit.

Group Type: EXPERIMENTAL

WL

Intervention Type: OTHER

Measuring change in weight

WL-Med

WL-Med will attend a one-hour, in-person session with a registered dietitian (RD) prior to the intervention. The RD will instruct on an eating pattern consistent with a MedDiet using an individualized exchange list. Exchanges are based on individual caloric needs to lose weight (WL-Med, calorie restriction to achieve a 1-2 lb. per week WL and 5% WL from baseline at 6 months). We will not ask subjects to abstain from alcohol despite its known effects on BA metabolism, but we will recommend that only 5% of calories come from alcohol taken with meals. Following the initial session, subjects will meet remotely or in-person for 24 individual sessions (1-hour, held approximately weekly). Additional asynchronous learning materials will be distributed weekly through a private Facebook group.

The WL-Med group will be prescribed an activity program. Some asynchronous lessons will contain information about physical activity. Physical activity will be monitored via FitBit.

Group Type: EXPERIMENTAL

Med

Intervention Type: OTHER

Mediterranean diet

WL

Intervention Type: OTHER

Measuring change in weight

Control

The study RD will meet individually with the Control group subjects in-person for 1-hour at the start of the 6-month intervention. Control participants will be instructed to maintain current eating and activity patterns and weight over the next 6 months. No dietary recommendations are provided, and they will receive weekly health newsletters that include non-diet related health topics (e.g., flu prevention). Contact will be made again at month-3 and post-intervention (month-6) research visits and during monthly phone calls to collect data pertaining to recent diet intake. At the month-3 assessment, weight will be checked and those with \>2.5% WL from baseline will receive additional instruction from the RD to maintain lifestyle patterns. All WL-Med materials are offered to the group in a self-guided format following the 6-month intervention.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Med

Mediterranean diet

Intervention Type: OTHER

WL

Measuring change in weight

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Men and women 45-75 years of age
• Self-identify as AA
• BMI 30-50 kg/m2
• Willingness to participate in all procedures including maintaining weight/current physical activity if randomized to Med-A/Control
• Willingness and ability to provide informed consent
• Willingness to be randomized
• Understands English
• Has access to a phone
• Plans to reside in Chicago for the next 8-10 months.

Exclusion Criteria

• renal disease
• autoimmune disorders
• immunodeficiency
• malabsorptive disorders
• significant gastrointestinal and/or hepatic diseases
• severe ischemic heart disease
• severe pulmonary disease
• history of bariatric surgery
• alcohol abuse (> 50 grams/day)
• illicit drug abuse (other than marijuana based on self-report)
• combustible tobacco use
• uncontrolled diabetes based on HbA1c>9.0%
• eating disorder
• cancer treatment within the past 12 months
• history of CRC
• genetic predisposition to CRC (e.g., Lynch syndrome)
• weight > 450 lbs. (weight limitation of the DXA scanner)
• currently adhering to a MedDiet based on a diet screener
• self-reported WL > 3% in the past 12 months
• currently on a WL diet or actively involved in a formal WL program (e.g., Weight Watchers)
• food allergies that would interfere with adopting a MedDiet
• antibiotic use in the past 3 months
• night-shift work
• regular use (i.e., ≥ 3 times per week) of prebiotics/probiotics/synbiotics, dietary fiber supplements, or laxatives,
• Gait disorder
• currently pregnant
• active Covid-19 infection within 6 weeks of recruitment/data collection.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Illinois at Chicago

OTHER

Sponsor Role: lead

Responsible Party

Lisa Tussing-Humphreys

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lisa Tussing-Humphreys, PhD, RD

Role: PRINCIPAL_INVESTIGATOR

University of Illinois at Chicago

Marian Fitzgibbon, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Illinois at Chicago

Locations

University of Illinois at Chicago

Chicago, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Lara Blumstein

Role: CONTACT

lbb@uic.edu

312-355-2328

Facility Contacts

Lisa Tussing-Humphreys

Role: primary

tussing@uic.edu

312-355-5521

References

McLeod A, Wolf P, Chapkin RS, Davidson LA, Ivanov I, Berbaum M, Williams LR, Gaskins HR, Ridlon J, Sanchez-Flack J, Blumstein L, Schiffer L, Hamm A, Cares K, Antonic M, Bernabe BP, Fitzgibbon M, Tussing-Humphreys L. Design of the Building Research in CRC prevention (BRIDGE-CRC) trial: a 6-month, parallel group Mediterranean diet and weight loss randomized controlled lifestyle intervention targeting the bile acid-gut microbiome axis to reduce colorectal cancer risk among African American/Black adults with obesity. Trials. 2023 Feb 15;24(1):113. doi: 10.1186/s13063-023-07115-4.

Reference Type: DERIVED

PMID: 36793105 (View on PubMed)

Other Identifiers

1R01CA250390-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2020-1342

Identifier Type: -

Identifier Source: org_study_id