Back to resultsWalnuts and Colon Health
Primary Purpose
Colorectal Cancer, Diet Habit
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Walnuts
Sponsored by
About this trial
This is an interventional prevention trial for Colorectal Cancer focused on measuring Colorectal cancer, Microbiome, Urolithin, Walnuts, Diet habit, Inflammatory markers, Colon inflammation
Eligibility Criteria
Inclusion Criteria:
Individuals in one of the following groups:
- Men and women between the ages of 40 to 75 years old, who are scheduled to undergo a routine screening or surveillance colonoscopy for colorectal cancer (CRC) and have a family history of CRC in a first degree relative diagnosed with CRC under the age of 65 years, or
- Men and women between the ages of 45 to 75 years old, who are referred for colonoscopy following a positive fecal immunochemical test (FIT) and have not had a high quality colonoscopy in the past 3 years, or
- Men and women between the ages of 45 to 75 years old, who have a personal history of colon polyps and are scheduled to undergo a surveillance colonoscopy
- Willing and able to provide written informed consent for study participation
- Willing to consume 2 ounces of walnuts daily for 3 weeks
- Willing to avoid intake of ellagic acid/ellagitannin-rich foods (e.g., pomegranates, hazelnuts, pistachios, strawberries, raspberries, blackberries, oak-aged wines, and other food on a list given by researchers) and fermented dairy products containing viable Bifidobacteria or Lactobacilli)
- Willing to stop taking dietary supplements, including probiotics
- Willing to have 2 separate blood draws, as well as urine and stool collections
- Willing to comply with all study requirements
Exclusion Criteria:
- Individual has a personal history of CRC, or a history of any malignancy (other than skin cancer) within the past 5 years
- Individual meets the Amsterdam criteria for Lynch Syndrome or has a history of familial adenomatous polyposis (FAP)
- Individual has been treated with immunosuppressive agents or systemic steroids, excluding inhalers, at least two weeks prior to the Screening Visit and for the duration of the study
- Use of antibiotics at least one month prior to the Screening Visit and for the duration of the study
- Patients with severe medical illness or those at high risk for anesthesia, as determined by good clinical practice
- Current evidence or previous history of ulcerative colitis or Crohn's disease
- Colonoscopy performed for reasons other than screening or surveillance for CRC
- HIV infection, chronic viral hepatitis
- Allergy to walnuts or hypersensitivity to tree nuts
- Peri-menopausal women with any chance or plan of pregnancy
- Individuals with blood coagulation disorders or on anti-coagulant therapy
- Any other condition that, in the opinion of the PI, might interfere with study objectives
- No race/ethnicity, language or gender exclusions for this study
Sites / Locations
- UConn HealthRecruiting
- Weill Cornell MedicineRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Walnut Consumption
Arm Description
Following enrollment, participants will start a 7-day wash-out period where they will be asked to avoid foods and beverages high in ellagitannins. These include pomegranates, hazelnuts, pistachios, walnuts (besides the samples given by the researchers), strawberries, raspberries, blackberries, oak-aged wines and spirits; a full list of foods and beverages to avoid will be provided. Then, participants will consume 2 ounces of walnuts daily with their usual diet while continuing to avoid ellagitannins for 21 days prior to their routine colonoscopy.
Outcomes
Primary Outcome Measures
Bacterial composition and taxonomy changes in the fecal microbiome
Bacterial composition and taxonomy changes in the fecal microbiome will be assessed using 16 Svedberg unit (16S) ribosomal ribonucleic acid (rRNA) sequencing, at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation).
Bacterial diversity changes and strain-level variations in the fecal microbiome
Bacterial diversity/abundance changes and strain-level variations in the fecal microbiome will be assessed using metagenomic shotgun sequencing at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation).
Bacterial gene expression profile changes in the fecal microbiome
Bacterial gene expression profile changes in the fecal microbiome will be assessed using metagenomic ribonucleic acid (RNA) sequencing at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation).
Urolithin levels in urine
Urolithin levels will be measured in urine by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry at day 0 (baseline/pre-washout), day 7 (post-washout/pre-walnut supplementation) and day 29 (post-walnut supplementation/end of study).
Association of urolithin levels with presence (and type) of colonic lesions
Baseline urolithin levels measured in the urine by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry will be associated with the presence (and type) of colonic lesions (e.g., advanced adenomas (AAs) or sessile serrated adenoma/polyps (SSA/Ps)) detected during the colonoscopy procedure at the end of the study (day 29).
Correlation of urolithin levels with fecal microbiome composition
Detailed statistical analyses will be used to correlate urolithin formation with the composition of the fecal microbiome at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation).
Correlation of colonic lesion gene expression with urolithin production
Colonic lesion (AAs and SSA/Ps) biopsies obtained at the end of the study (day 29) during the colonoscopy procedure will undergo DNA sequence-based analysis to determine gene expression profiling. These results will be compared to urinary urolithin levels measured at baseline to establish correlations between urolithin production and colorectal cancer risk markers.
Secondary Outcome Measures
Short-chain fatty acid composition in stool
Short-chain fatty acids in freeze-dried stool samples will be measured using differential mobility separation at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation).
Bile acid metabolism in stool
Primary and secondary bile acids in freeze-dried stool samples will be analyzed using standard liquid chromatography-mass spectrometry methods at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation).
Inflammatory markers in blood
Markers of systemic inflammation associated with adenoma risk will be measured in plasma using commercial enzyme-linked immunoassay (ELISA) kits at day 7 (post-washout/pre-walnut supplementation) and at day 29 (end of study).
Correlation of dietary behavior with presence (or absence) of colonic polyps
Overall diet quality and habits documented on brief food questionnaires will be analyzed by NutritionQuest at day 7 (post-washout/pre-walnut supplementation). Dietary behavior data will be correlated with the presence or absence of colonic polyps detected during the colonoscopy procedure at the end of the study (day 29).
Correlation of dietary behavior with fecal microbiome composition and diversity
Dietary behavior data documented on 3-day dietary records will be analyzed by Nutrition Data System for Research software. This data will be correlated with fecal microbiome composition and diversity at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation).
Correlation of dietary behavior with urolithin production
Dietary behavior data documented on 3-day dietary records will be analyzed by Nutrition Data System for Research software. This data will be correlated with urolithin levels at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation).
Full Information
NCT ID
NCT05195970
First Posted
November 24, 2021
Last Updated
November 15, 2022
Sponsor
UConn Health
Collaborators
National Institutes of Health (NIH), National Cancer Institute (NCI), Weill Medical College of Cornell University, University of Connecticut, The Jackson Laboratory for Genomic Medicine, California Walnut Commission, Spanish National Research Council
1. Study Identification
Unique Protocol Identification Number
NCT05195970
Brief Title
Walnuts and Colon Health
Official Title
Microbiota, Metabolites and Colon Neoplasia
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 24, 2022 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
UConn Health
Collaborators
National Institutes of Health (NIH), National Cancer Institute (NCI), Weill Medical College of Cornell University, University of Connecticut, The Jackson Laboratory for Genomic Medicine, California Walnut Commission, Spanish National Research Council
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this research study is to examine whether adding walnuts to your diet can have a beneficial effect on the gut bacteria population, inflammatory markers in the blood, and the tissue that lines the inside of the colon.
Detailed Description
This is a 29-day dietary intervention study where participants will be asked to consume 2 ounces of walnuts daily for 21 days, and at the end of the study period they will come in for a routine colonoscopy. After being informed about the study and potential risks, participants giving written informed consent will first start a 7-day wash-out period where they will be asked to avoid foods high in ellagitannins for the duration of the study. In addition, participants will be asked to complete food and activity questionnaires, a walnut consumption log, and two sets of 3-day dietary records during their participation in the study. Participants will also be asked to provide three urine samples, two blood samples, and two stool samples at multiple time points, and 8-10 colon tissue specimens (biopsies) will be collected during their colonoscopy procedure for the purposes of this study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Diet Habit
Keywords
Colorectal cancer, Microbiome, Urolithin, Walnuts, Diet habit, Inflammatory markers, Colon inflammation
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Walnut Consumption
Arm Type
Experimental
Arm Description
Following enrollment, participants will start a 7-day wash-out period where they will be asked to avoid foods and beverages high in ellagitannins. These include pomegranates, hazelnuts, pistachios, walnuts (besides the samples given by the researchers), strawberries, raspberries, blackberries, oak-aged wines and spirits; a full list of foods and beverages to avoid will be provided. Then, participants will consume 2 ounces of walnuts daily with their usual diet while continuing to avoid ellagitannins for 21 days prior to their routine colonoscopy.
Intervention Type
Other
Intervention Name(s)
Walnuts
Intervention Description
Participants consume 2 ounces of walnuts daily for 21 days
Primary Outcome Measure Information:
Title
Bacterial composition and taxonomy changes in the fecal microbiome
Description
Bacterial composition and taxonomy changes in the fecal microbiome will be assessed using 16 Svedberg unit (16S) ribosomal ribonucleic acid (rRNA) sequencing, at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation).
Time Frame
Day 7 and Day 28
Title
Bacterial diversity changes and strain-level variations in the fecal microbiome
Description
Bacterial diversity/abundance changes and strain-level variations in the fecal microbiome will be assessed using metagenomic shotgun sequencing at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation).
Time Frame
Day 7 and Day 28
Title
Bacterial gene expression profile changes in the fecal microbiome
Description
Bacterial gene expression profile changes in the fecal microbiome will be assessed using metagenomic ribonucleic acid (RNA) sequencing at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation).
Time Frame
Day 7 and Day 28
Title
Urolithin levels in urine
Description
Urolithin levels will be measured in urine by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry at day 0 (baseline/pre-washout), day 7 (post-washout/pre-walnut supplementation) and day 29 (post-walnut supplementation/end of study).
Time Frame
Day 0, Day 7 and Day 29
Title
Association of urolithin levels with presence (and type) of colonic lesions
Description
Baseline urolithin levels measured in the urine by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry will be associated with the presence (and type) of colonic lesions (e.g., advanced adenomas (AAs) or sessile serrated adenoma/polyps (SSA/Ps)) detected during the colonoscopy procedure at the end of the study (day 29).
Time Frame
Day 29
Title
Correlation of urolithin levels with fecal microbiome composition
Description
Detailed statistical analyses will be used to correlate urolithin formation with the composition of the fecal microbiome at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation).
Time Frame
Day 7 and Day 28
Title
Correlation of colonic lesion gene expression with urolithin production
Description
Colonic lesion (AAs and SSA/Ps) biopsies obtained at the end of the study (day 29) during the colonoscopy procedure will undergo DNA sequence-based analysis to determine gene expression profiling. These results will be compared to urinary urolithin levels measured at baseline to establish correlations between urolithin production and colorectal cancer risk markers.
Time Frame
Day 29
Secondary Outcome Measure Information:
Title
Short-chain fatty acid composition in stool
Description
Short-chain fatty acids in freeze-dried stool samples will be measured using differential mobility separation at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation).
Time Frame
Day 7 and Day 28
Title
Bile acid metabolism in stool
Description
Primary and secondary bile acids in freeze-dried stool samples will be analyzed using standard liquid chromatography-mass spectrometry methods at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation).
Time Frame
Day 7 and Day 28
Title
Inflammatory markers in blood
Description
Markers of systemic inflammation associated with adenoma risk will be measured in plasma using commercial enzyme-linked immunoassay (ELISA) kits at day 7 (post-washout/pre-walnut supplementation) and at day 29 (end of study).
Time Frame
Day 7 and Day 29
Title
Correlation of dietary behavior with presence (or absence) of colonic polyps
Description
Overall diet quality and habits documented on brief food questionnaires will be analyzed by NutritionQuest at day 7 (post-washout/pre-walnut supplementation). Dietary behavior data will be correlated with the presence or absence of colonic polyps detected during the colonoscopy procedure at the end of the study (day 29).
Time Frame
Day 7 and Day 29
Title
Correlation of dietary behavior with fecal microbiome composition and diversity
Description
Dietary behavior data documented on 3-day dietary records will be analyzed by Nutrition Data System for Research software. This data will be correlated with fecal microbiome composition and diversity at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation).
Time Frame
Day 7 and Day 28
Title
Correlation of dietary behavior with urolithin production
Description
Dietary behavior data documented on 3-day dietary records will be analyzed by Nutrition Data System for Research software. This data will be correlated with urolithin levels at day 7 (post-washout/pre-walnut supplementation) and at day 28 (post-walnut supplementation).
Time Frame
Day 7 and Day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Individuals in one of the following groups:
Men and women between the ages of 40 to 75 years old, who are scheduled to undergo a routine screening or surveillance colonoscopy for colorectal cancer (CRC) and have a family history of CRC in a first degree relative diagnosed with CRC under the age of 65 years, or
Men and women between the ages of 45 to 75 years old, who are referred for colonoscopy following a positive fecal immunochemical test (FIT) and have not had a high quality colonoscopy in the past 3 years, or
Men and women between the ages of 45 to 75 years old, who have a personal history of colon polyps and are scheduled to undergo a surveillance colonoscopy
Willing and able to provide written informed consent for study participation
Willing to consume 2 ounces of walnuts daily for 3 weeks
Willing to avoid intake of ellagic acid/ellagitannin-rich foods (e.g., pomegranates, hazelnuts, pistachios, strawberries, raspberries, blackberries, oak-aged wines, and other food on a list given by researchers) and fermented dairy products containing viable Bifidobacteria or Lactobacilli)
Willing to stop taking dietary supplements, including probiotics
Willing to have 2 separate blood draws, as well as urine and stool collections
Willing to comply with all study requirements
Exclusion Criteria:
Individual has a personal history of CRC, or a history of any malignancy (other than skin cancer) within the past 5 years
Individual meets the Amsterdam criteria for Lynch Syndrome or has a history of familial adenomatous polyposis (FAP)
Individual has been treated with immunosuppressive agents or systemic steroids, excluding inhalers, at least two weeks prior to the Screening Visit and for the duration of the study
Use of antibiotics at least one month prior to the Screening Visit and for the duration of the study
Patients with severe medical illness or those at high risk for anesthesia, as determined by good clinical practice
Current evidence or previous history of ulcerative colitis or Crohn's disease
Colonoscopy performed for reasons other than screening or surveillance for CRC
HIV infection, chronic viral hepatitis
Allergy to walnuts or hypersensitivity to tree nuts
Peri-menopausal women with any chance or plan of pregnancy
Individuals with blood coagulation disorders or on anti-coagulant therapy
Any other condition that, in the opinion of the PI, might interfere with study objectives
No race/ethnicity, language or gender exclusions for this study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nuoxi Fan
Phone
860-679-8703
Email
nfan@uchc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Slawa Gajewska
Phone
860-679-2939
Email
gajewska@uchc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel W. Rosenberg, Ph.D.
Organizational Affiliation
UConn Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
UConn Health
City
Farmington
State/Province
Connecticut
ZIP/Postal Code
06032
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nuoxi Fan
Phone
860-679-8703
Email
nfan@uchc.edu
First Name & Middle Initial & Last Name & Degree
Slawa Gajewska
Phone
860-679-2939
Email
gajewska@uchc.edu
First Name & Middle Initial & Last Name & Degree
Daniel W. Rosenberg, Ph.D.
First Name & Middle Initial & Last Name & Degree
John W. Birk, M.D.
First Name & Middle Initial & Last Name & Degree
Haleh Vaziri, M.D.
Facility Name
Weill Cornell Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kevin Yeung
Phone
917-250-0889
Email
key4001@med.cornell.edu
First Name & Middle Initial & Last Name & Degree
Steven M. Lipkin, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
Felice Schnoll-Sussman, M.D.
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
31137456
Citation
Nakanishi M, Matz A, Klemashevich C, Rosenberg DW. Dietary Walnut Supplementation Alters Mucosal Metabolite Profiles During DSS-Induced Colonic Ulceration. Nutrients. 2019 May 20;11(5):1118. doi: 10.3390/nu11051118.
Results Reference
background
PubMed Identifier
31818852
Citation
Chen Y, Nakanishi M, Bautista EJ, Qendro V, Sodergren E, Rosenberg DW, Weinstock GM. Colon Cancer Prevention with Walnuts: A Longitudinal Study in Mice from the Perspective of a Gut Enterotype-like Cluster. Cancer Prev Res (Phila). 2020 Jan;13(1):15-24. doi: 10.1158/1940-6207.CAPR-19-0273. Epub 2019 Dec 9.
Results Reference
background
PubMed Identifier
27215566
Citation
Nakanishi M, Chen Y, Qendro V, Miyamoto S, Weinstock E, Weinstock GM, Rosenberg DW. Effects of Walnut Consumption on Colon Carcinogenesis and Microbial Community Structure. Cancer Prev Res (Phila). 2016 Aug;9(8):692-703. doi: 10.1158/1940-6207.CAPR-16-0026. Epub 2016 May 23.
Results Reference
background
PubMed Identifier
31754633
Citation
Hong BY, Ideta T, Lemos BS, Igarashi Y, Tan Y, DiSiena M, Mo A, Birk JW, Forouhar F, Devers TJ, Weinstock GM, Rosenberg DW. Characterization of Mucosal Dysbiosis of Early Colonic Neoplasia. NPJ Precis Oncol. 2019 Nov 14;3:29. doi: 10.1038/s41698-019-0101-6. eCollection 2019.
Results Reference
background
PubMed Identifier
27158799
Citation
Tomas-Barberan FA, Gonzalez-Sarrias A, Garcia-Villalba R, Nunez-Sanchez MA, Selma MV, Garcia-Conesa MT, Espin JC. Urolithins, the rescue of "old" metabolites to understand a "new" concept: Metabotypes as a nexus among phenolic metabolism, microbiota dysbiosis, and host health status. Mol Nutr Food Res. 2017 Jan;61(1). doi: 10.1002/mnfr.201500901. Epub 2016 Jun 20.
Results Reference
background
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Walnuts and Colon Health
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