Skip to main content
OpenTrials
Completed

NCT Number: NCT04753359

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Colorectal Cancer Behavior Behavior, Animal Colonic Diseases Colorectal Neoplasms Diet Habit Digestive System Diseases Digestive System Neoplasms Feeding Behavior Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases

Age range

45 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Med

Other

Mediterranean diet

WL

Other

Measuring change in weight

Primary outcomes

  1. Circulating and fecal bile acids

    Time frame: baseline

    Absolute measurement of BAs in stool and serum obtained at baseline will be performed under the direction of Co-I Ridlon. Samples will be extracted, and supernatants will be dried and resuspended for LC/MS analysis following validated and published methods. We will quantify all major primary and secondary BAs (e.g., DCA) and glycine and taurine conjugates and their ratios, as well as total BAs and total unconjugated BAs. Authentic reference BAs will be purchased from Sigma-Aldrich and Steraloids. Blind duplicate samples will be used to assess inter- and intra-batch precision.

  2. Circulating and fecal bile acids

    Time frame: 3 month

    Absolute measurement of BAs in stool and serum obtained at mid-study (3 month follow up) will be performed under the direction of Co-I Ridlon. Samples will be extracted, and supernatants will be dried and resuspended for LC/MS analysis following validated and published methods. We will quantify all major primary and secondary BAs (e.g., DCA) and glycine and taurine conjugates and their ratios, as well as total BAs and total unconjugated BAs. Authentic reference BAs will be purchased from Sigma-Aldrich and Steraloids. Blind duplicate samples will be used to assess inter- and intra-batch precision.

  3. Circulating and fecal bile acids

    Time frame: 6 month

    Absolute measurement of BAs in stool and serum obtained at post-intervention (6 month follow up) will be performed under the direction of Co-I Ridlon. Samples will be extracted, and supernatants will be dried and resuspended for LC/MS analysis following validated and published methods. We will quantify all major primary and secondary BAs (e.g., DCA) and glycine and taurine conjugates and their ratios, as well as total BAs and total unconjugated BAs. Authentic reference BAs will be purchased from Sigma-Aldrich and Steraloids. Blind duplicate samples will be used to assess inter- and intra-batch precision.

  4. Gut microbiota for metabolic function

    Time frame: baseline

    The UIC Genomics core will PCR amplify genomic DNA with primers CS1_515F and CS2_806R (modified from the set used by the Earth Microbiome Project) targeting the V4 region of microbial small subunit ribosomal RNA genes. Amplicons will be generated using a two-stage PCR protocol. The V4 region of the 16S rRNA gene will be sequenced with the Illumina MiSeq platform to generate 2x250 bp paired end reads per sample. Environmental controls will be included in the sequences to distinguish from any contaminants in reagents or the lab environment.

  5. Gut microbiota for metabolic function

    Time frame: 3 month

    The UIC Genomics core will PCR amplify genomic DNA with primers CS1_515F and CS2_806R (modified from the set used by the Earth Microbiome Project) targeting the V4 region of microbial small subunit ribosomal RNA genes. Amplicons will be generated using a two-stage PCR protocol. The V4 region of the 16S rRNA gene will be sequenced with the Illumina MiSeq platform to generate 2x250 bp paired end reads per sample. Environmental controls will be included in the sequences to distinguish from any contaminants in reagents or the lab environment.

  6. Gut microbiota for metabolic function

    Time frame: 6 month

    The UIC Genomics core will PCR amplify genomic DNA with primers CS1_515F and CS2_806R (modified from the set used by the Earth Microbiome Project) targeting the V4 region of microbial small subunit ribosomal RNA genes. Amplicons will be generated using a two-stage PCR protocol. The V4 region of the 16S rRNA gene will be sequenced with the Illumina MiSeq platform to generate 2x250 bp paired end reads per sample. Environmental controls will be included in the sequences to distinguish from any contaminants in reagents or the lab environment.

  7. Gene expression

    Time frame: baseline

    From stool preserved in Ambion Denaturation Solution, eukaryotic polyA+ RNA will be isolated using the Active Motif mTRAP Maxi kit followed by DNA removal with DNAFree (Invitrogen). Libraries will be quantified using the Library Quantification kit (Kapa Biosystems), and sequencing will be performed on an Illumina HiSeq 2500 platform using standard Illumina protocols. RNA reads will be mapped with the STAR aligner using the default parameters to the Ensembl GRCh38 human reference. Reads will be examined for quality control using FastQC and quantified using HTSeq-count. Sequencing reads will be filtered to remove genes present in low abundance. For stool exfoliated cells, the RNA-seq gene count matrix is very sparse, with most entries corresponding to zero transcripts; thus, genes in stool will be removed if >33% of the samples contain only 0 or 1 read.

  8. Gene expression

    Time frame: 3 month

    From stool preserved in Ambion Denaturation Solution, eukaryotic polyA+ RNA will be isolated using the Active Motif mTRAP Maxi kit followed by DNA removal with DNAFree (Invitrogen). Libraries will be quantified using the Library Quantification kit (Kapa Biosystems), and sequencing will be performed on an Illumina HiSeq 2500 platform using standard Illumina protocols. RNA reads will be mapped with the STAR aligner using the default parameters to the Ensembl GRCh38 human reference. Reads will be examined for quality control using FastQC and quantified using HTSeq-count. Sequencing reads will be filtered to remove genes present in low abundance. For stool exfoliated cells, the RNA-seq gene count matrix is very sparse, with most entries corresponding to zero transcripts; thus, genes in stool will be removed if >33% of the samples contain only 0 or 1 read.

  9. Gene expression

    Time frame: 6 month

    From stool preserved in Ambion Denaturation Solution, eukaryotic polyA+ RNA will be isolated using the Active Motif mTRAP Maxi kit followed by DNA removal with DNAFree (Invitrogen). Libraries will be quantified using the Library Quantification kit (Kapa Biosystems), and sequencing will be performed on an Illumina HiSeq 2500 platform using standard Illumina protocols. RNA reads will be mapped with the STAR aligner using the default parameters to the Ensembl GRCh38 human reference. Reads will be examined for quality control using FastQC and quantified using HTSeq-count. Sequencing reads will be filtered to remove genes present in low abundance. For stool exfoliated cells, the RNA-seq gene count matrix is very sparse, with most entries corresponding to zero transcripts; thus, genes in stool will be removed if >33% of the samples contain only 0 or 1 read.

  10. Exfoliated intestinal epithelial cell transcriptomics

    Time frame: Baseline

    Exfoliated intestinal epithelial cells separated from stool with gene expression analysis

  11. Exfoliated intestinal epithelial cell transcriptomics

    Time frame: 3 months

    Exfoliated intestinal epithelial cells separated from stool with gene expression analysis

  12. Exfoliated intestinal epithelial cell transcriptomics

    Time frame: 6 months

    Exfoliated intestinal epithelial cells separated from stool with gene expression analysis

Secondary outcomes

  1. Body weight

    Time frame: baseline

    Body weight will be measured with a digital scale

  2. Body weight

    Time frame: 3 month

    Body weight will be measured with a digital scale

  3. Body weight

    Time frame: 6 month

    Body weight will be measured with a digital scale

  4. Body mass index

    Time frame: baseline

    Calculated from measured weight and height

  5. Body mass index

    Time frame: 3 month

    Calculated from measured weight and height

  6. Body mass index

    Time frame: 6 month

    Calculated from measured weight and height

  7. Mediterranean Diet Adherence

    Time frame: Baseline

    Measured with a food frequency questionnaire, 24-hour diet recalls, and screener which will be aggregated to evaluate a total adherence score

  8. Mediterranean Diet Adherence

    Time frame: Month 1

    Measured with a food frequency questionnaire, 24-hour diet recalls, and screener which will be aggregated to evaluate a total adherence score

  9. Mediterranean Diet Adherence

    Time frame: Month 2

    Measured with a food frequency questionnaire, 24-hour diet recalls, and screener which will be aggregated to evaluate a total adherence score

  10. Mediterranean Diet Adherance

    Time frame: Month 3

    Measured with a food frequency questionnaire, 24-hour diet recalls, and screener which will be aggregated to evaluate a total adherence score

  11. Mediterranean Diet Adherence

    Time frame: Month 4

    Measured with a food frequency questionnaire, 24-hour diet recalls, and screener which will be aggregated to evaluate a total adherence score

  12. Mediterranean Diet Adherence

    Time frame: Month 5

    Measured with a food frequency questionnaire, 24-hour diet recalls, and screener which will be aggregated to evaluate a total adherence score

  13. Mediterranean Diet Adherence

    Time frame: Month 6

    Measured with a food frequency questionnaire, 24-hour diet recalls, and screener which will be aggregated to evaluate a total adherence score

  14. Physical activity

    Time frame: Baseline

    Number of steps measured for 7-days with FitBit wearable tracker

  15. Physical activity

    Time frame: 3 month

    Number of steps measured for 7-days with FitBit wearable tracker

  16. Physical activity

    Time frame: 6 month

    Number of steps measured for 7-days with FitBit wearable tracker

  17. Total and regional body composition (fat and muscle)

    Time frame: baseline

    DXA whole-body composition scan to measure total body composition fat% vs bone% vs lean%

  18. Total and regional body composition (fat and muscle)

    Time frame: 3 month

    DXA whole-body composition scan to measure total body composition fat% vs bone% vs lean%

  19. Total and regional body composition (fat and muscle)

    Time frame: 6 month

    DXA whole-body composition scan to measure total body composition fat% vs bone% vs lean%

  20. Circulating cytokines

    Time frame: Baseline

    Measured from serum using a commercial multiplex kit

  21. Circulating cytokines

    Time frame: 3 month

    Measured from serum using a commercial multiplex kit

  22. Circulating cytokines

    Time frame: 6 month

    Measured from serum using a commercial multiplex kit

  23. Fasting glucose

    Time frame: Baseline

    Measured from plasma at a local commercial lab

  24. Fasting glucose

    Time frame: 3 month

    Measured from plasma at a local commercial lab

  25. Fasting glucose

    Time frame: 6 month

    Measured from plasma at a local commercial lab

  26. Fasting insulin

    Time frame: Baseline

    Measured from plasma at a local commercial lab

  27. Fasting insulin

    Time frame: 3 month

    Measured from plasma at a local commercial lab

  28. Fasting insulin

    Time frame: 6 month

    Measured from plasma at a local commercial lab

Other outcomes

  1. Adverse events

    Time frame: Through study completion, an average of 6 months

    Obtained via interview

  2. Psychosocial health

    Time frame: Baseline

    survey

  3. Psychosocial health

    Time frame: 3 month

    survey

  4. Psychosocial health

    Time frame: 6 month

    survey

  5. Medication use

    Time frame: baseline

    Survey, interview

  6. Medication use

    Time frame: 3 month

    Survey, interview

  7. Medication use

    Time frame: 6 month

    Survey, interview

  8. Bowel habits

    Time frame: baseline

    survey

  9. Bowel habits

    Time frame: 3 month

    survey

  10. Bowel habits

    Time frame: 6 month

    survey

Sponsors and collaborators

Lead sponsor

University of Illinois at Chicago

Other

Collaborators

  • National Cancer Institute (NCI)

Registry information

Acronym: Bridge CRC

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Feb 15, 2021
Registry last updated
May 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.