Walnuts and Colon Health

Colorectal Cancer Clinical Trial

Official title:

Microbiota, Metabolites and Colon Neoplasia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05195970
• Other study ID #: 21-167JS-1
• Secondary ID: 1R01CA252045-01A
• Status: Recruiting
• Phase: N/A
• Start date: January 24, 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: March 2024
• Source: UConn Health
• Contact: Nuoxi Fan
• Phone: 860-679-8703
• Email: nfan[@]uchc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 39 Years to 75 Years

Eligibility

Inclusion Criteria:

• Men and women between the ages of 39-75 years old who meet the criteria of one of the following groups and are eligible to undergo a routine screening or surveillance colonoscopy for colorectal cancer (CRC):

1. Individuals who have a family history of CRC in a first-degree relative diagnosed with CRC under the age of 65 years, or

2. Individuals who are referred for colonoscopy following a positive fecal immunochemical test (FIT) or a positive Cologuard screening test and have not had a high-quality colonoscopy in the past 3 years, or

3. Individuals who have a personal history of colon polyps

• Willing and able to provide written informed consent for study participation

• Willing to consume 2 ounces (56 grams) of walnuts daily for 3 weeks

• Willing to avoid intake of EA/ET-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 two separate blood draws, as well as urine and stool collections

• Willingness 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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Diet Habit

Intervention

Other:
• Walnuts
Participants consume 2 ounces of walnuts daily for 21 days

Locations

Country	Name	City	State
United States	UConn Health	Farmington	Connecticut
United States	Weill Cornell Medicine	New York	New York

Sponsors (8)

Lead Sponsor	Collaborator
UConn Health	California Walnut Commission, National Cancer Institute (NCI), National Institutes of Health (NIH), Spanish National Research Council, University of Connecticut, University of Florida, Weill Medical College of Cornell University

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Day 7 and Day 28
Primary	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).	Day 7 and Day 28
Primary	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).	Day 7 and Day 28
Primary	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).	Day 0, Day 7 and Day 29
Primary	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).	Day 29
Primary	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).	Day 7 and Day 28
Primary	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.	Day 29
Secondary	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).	Day 7 and Day 28
Secondary	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).	Day 7 and Day 28
Secondary	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).	Day 7 and Day 29
Secondary	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).	Day 7 and Day 29
Secondary	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).	Day 7 and Day 28
Secondary	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).	Day 7 and Day 28