Colorectal CancerBridge CRCNCT04753359
Mediterranean Diet and Weight Loss: Targeting the Bile Acid/Gut Microbiome Axis to Reduce Colorectal Cancer
A study testing Med and WL in people with Colorectal Cancer and Diet Habit, run by University of Illinois Chicago at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Colorectal Cancer, Diet Habit
- What is being tested?
- Med and WL
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 180 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2022to 31 Jul 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- Understands English
- Has access to a phone
- Plans to reside in Chicago for the next 8-10 months.
Who cannot join
- renal disease
- autoimmune disorders
- immunodeficiency
- malabsorptive disorders
- significant gastrointestinal and/or hepatic diseases
- severe ischemic heart disease
Show all 27Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Illinois at Chicago
Chicago, Illinois, 60612
About this study
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.
Read the 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
- Being tested
- Med, WL
- Medical subject headings
- Colorectal Neoplasms, Feeding Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MedOther
Mediterranean diet
WLOther
Measuring change in weight
| Study group | Role | What they receive |
|---|---|---|
| Med-A | Experimental | 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. Receives: Other: Med |
| WL-A | Experimental | 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. Receives: Other: WL |
| WL-Med | Experimental | 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. Receives: Other: Med; Other: WL |
| Control | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Circulating and fecal bile acids
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.
Measured: baseline
Circulating and fecal bile acids
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.
Measured: 3 month
Circulating and fecal bile acids
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.
Measured: 6 month
Gut microbiota for metabolic function
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.
Measured: baseline
Gut microbiota for metabolic function
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.
Measured: 3 month
Gut microbiota for metabolic function
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.
Measured: 6 month
Gene expression
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.
Measured: baseline
Gene expression
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.
Measured: 3 month
Gene expression
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.
Measured: 6 month
Exfoliated intestinal epithelial cell transcriptomics
Exfoliated intestinal epithelial cells separated from stool with gene expression analysis
Measured: Baseline
Exfoliated intestinal epithelial cell transcriptomics
Exfoliated intestinal epithelial cells separated from stool with gene expression analysis
Measured: 3 months
Exfoliated intestinal epithelial cell transcriptomics
Exfoliated intestinal epithelial cells separated from stool with gene expression analysis
Measured: 6 months
Secondary outcomes (28)
Body weight
Body weight will be measured with a digital scale
Measured: baseline
Body weight
Body weight will be measured with a digital scale
Measured: 3 month
Body weight
Body weight will be measured with a digital scale
Measured: 6 month
Body mass index
Calculated from measured weight and height
Measured: baseline
Body mass index
Calculated from measured weight and height
Measured: 3 month
Body mass index
Calculated from measured weight and height
Measured: 6 month
Mediterranean Diet Adherence
Measured with a food frequency questionnaire, 24-hour diet recalls, and screener which will be aggregated to evaluate a total adherence score
Measured: Baseline
Mediterranean Diet Adherence
Measured with a food frequency questionnaire, 24-hour diet recalls, and screener which will be aggregated to evaluate a total adherence score
Measured: Month 1
Mediterranean Diet Adherence
Measured with a food frequency questionnaire, 24-hour diet recalls, and screener which will be aggregated to evaluate a total adherence score
Measured: Month 2
Mediterranean Diet Adherance
Measured with a food frequency questionnaire, 24-hour diet recalls, and screener which will be aggregated to evaluate a total adherence score
Measured: Month 3
Mediterranean Diet Adherence
Measured with a food frequency questionnaire, 24-hour diet recalls, and screener which will be aggregated to evaluate a total adherence score
Measured: Month 4
Mediterranean Diet Adherence
Measured with a food frequency questionnaire, 24-hour diet recalls, and screener which will be aggregated to evaluate a total adherence score
Measured: Month 5
Mediterranean Diet Adherence
Measured with a food frequency questionnaire, 24-hour diet recalls, and screener which will be aggregated to evaluate a total adherence score
Measured: Month 6
Physical activity
Number of steps measured for 7-days with FitBit wearable tracker
Measured: Baseline
Physical activity
Number of steps measured for 7-days with FitBit wearable tracker
Measured: 3 month
Physical activity
Number of steps measured for 7-days with FitBit wearable tracker
Measured: 6 month
Total and regional body composition (fat and muscle)
DXA whole-body composition scan to measure total body composition fat% vs bone% vs lean%
Measured: baseline
Total and regional body composition (fat and muscle)
DXA whole-body composition scan to measure total body composition fat% vs bone% vs lean%
Measured: 3 month
Total and regional body composition (fat and muscle)
DXA whole-body composition scan to measure total body composition fat% vs bone% vs lean%
Measured: 6 month
Circulating cytokines
Measured from serum using a commercial multiplex kit
Measured: Baseline
Circulating cytokines
Measured from serum using a commercial multiplex kit
Measured: 3 month
Circulating cytokines
Measured from serum using a commercial multiplex kit
Measured: 6 month
Fasting glucose
Measured from plasma at a local commercial lab
Measured: Baseline
Fasting glucose
Measured from plasma at a local commercial lab
Measured: 3 month
Fasting glucose
Measured from plasma at a local commercial lab
Measured: 6 month
Fasting insulin
Measured from plasma at a local commercial lab
Measured: Baseline
Fasting insulin
Measured from plasma at a local commercial lab
Measured: 3 month
Fasting insulin
Measured from plasma at a local commercial lab
Measured: 6 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2021
- Study start1 Feb 2022
- Primary completion31 Jul 2025
- Study completion31 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by University of Illinois ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study is a four-arm RCT designed to test the effect of a weight-stable MedDiet alone (Med-A) lifestyle intervention, calorie restriction for WL with no diet composition change (WL-A) intervention, a MedDiet WL lifestyle intervention (WL-Med) compared to Control on BA metabolism, the gut microbiome, and gene expression in exfoliated intestinal epithelial cells. The study includes 1) screening potential subjects; 2) baseline assessment of diet, lifestyle behaviors (e.g., physical activity), anthropometrics, and blood and fecal sampling; 3) a four-arm RCT; and 4) mid-(month 3) and post-intervention (month 6) assessments.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Illinois Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Dr. Fitzgibbon, University of Illinois Chicago
- Investigators
- Marian Fitzgibbon, PhD, Principal investigator, University of Illinois ChicagoLisa Tussing-Humphreys, PhD, RD, Principal investigator, University of Illinois Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04753359
- Sponsor's protocol ID
- 2020-1342
- Other IDs
- 1R01CA250390-01A1
- Acronym
- Bridge CRC
- Status last verified
- May 2026
- First submitted
- 29 Jan 2021
- Last updated
- 27 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 36793105
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mediterranean Diet and Weight Loss: Targeting the Bile Acid/Gut Microbiome Axis to Reduce Colorectal Cancer
- ClinicalTrials.gov ID
- NCT04753359
- Acronym / sponsor ID
- Bridge CRC / 2020-1342
- Conditions
- Colorectal Cancer, Diet Habit
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- University of Illinois ChicagoUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- 31 Jul 2025 (actual)
- Study completion
- 31 Jul 2025 (actual)
- First posted
- 15 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
- Model description
- This study is a four-arm RCT designed to test the effect of a weight-stable MedDiet alone (Med-A) lifestyle intervention, calorie restriction for WL with no diet composition change (WL-A) intervention, a MedDiet WL lifestyle intervention (WL-Med) compared to Control on BA metabolism, the gut microbiome, and gene expression in exfoliated intestinal epithelial cells. The study includes 1) screening potential subjects; 2) baseline assessment of diet, lifestyle behaviors (e.g., physical activity), anthropometrics, and blood and fecal sampling; 3) a four-arm RCT; and 4) mid-(month 3) and post-intervention (month 6) assessments.
| Arm | Type | Receives |
|---|---|---|
| Med-A | Experimental | Other: MedMed-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. |
| WL-A | Experimental | Other: WLWL-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. |
| WL-Med | Experimental | Other: Med, Other: WLWL-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. |
| Control | No intervention | –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. |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (27 listed)
- renal disease
- autoimmune disorders
- immunodeficiency
- malabsorptive disorders
- significant gastrointestinal and/or hepatic diseases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MedMediterranean diet | Other | Med-A, WL-Med |
| WLMeasuring change in weight | Other | WL-A, WL-Med |
Primary outcome
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.
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.
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.
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.
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.
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.
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.
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.
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.
Exfoliated intestinal epithelial cell transcriptomics
Time frame: Baseline
Exfoliated intestinal epithelial cells separated from stool with gene expression analysis
Exfoliated intestinal epithelial cell transcriptomics
Time frame: 3 months
Exfoliated intestinal epithelial cells separated from stool with gene expression analysis
Exfoliated intestinal epithelial cell transcriptomics
Time frame: 6 months
Exfoliated intestinal epithelial cells separated from stool with gene expression analysis
28 secondary outcomes
Body weight
Time frame: baseline
Body weight
Time frame: 3 month
Body weight
Time frame: 6 month
Body mass index
Time frame: baseline
Body mass index
Time frame: 3 month
Body mass index
Time frame: 6 month
Mediterranean Diet Adherence
Time frame: Baseline
Mediterranean Diet Adherence
Time frame: Month 1
Mediterranean Diet Adherence
Time frame: Month 2
Mediterranean Diet Adherance
Time frame: Month 3
Mediterranean Diet Adherence
Time frame: Month 4
Mediterranean Diet Adherence
Time frame: Month 5
Mediterranean Diet Adherence
Time frame: Month 6
Physical activity
Time frame: Baseline
Physical activity
Time frame: 3 month
Physical activity
Time frame: 6 month
Total and regional body composition (fat and muscle)
Time frame: baseline
Total and regional body composition (fat and muscle)
Time frame: 3 month
Total and regional body composition (fat and muscle)
Time frame: 6 month
Circulating cytokines
Time frame: Baseline
Circulating cytokines
Time frame: 3 month
Circulating cytokines
Time frame: 6 month
Fasting glucose
Time frame: Baseline
Fasting glucose
Time frame: 3 month
Fasting glucose
Time frame: 6 month
Fasting insulin
Time frame: Baseline
Fasting insulin
Time frame: 3 month
Fasting insulin
Time frame: 6 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2026.
- Derived from this study: PubMed 36793105McLeod 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marian Fitzgibbon, PhD principal investigator
University of Illinois Chicago
Lisa Tussing-Humphreys, PhD, RD principal investigator
University of Illinois Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Med and WL in people with Colorectal Cancer and Diet Habit, run by University of Illinois Chicago at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Circulating and fecal bile acids (time frame: baseline). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04753359, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2026.