Ellagic Acid, Urolithin and Colonic Microbial Communities Affected by Walnut Consumption

NCT04066816 | Completed DMC

• 1 other identifier: 19-121JS-1
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

Briefly, this is a 28-day dietary intervention study participants will be asked to eat 2 ounces (52 grams) of walnuts every day for 3 weeks, and at the end of the study period they will come in for a colonoscopy. Participants will first start a 1-week run-in period where they will be asked to avoid foods high in ellagic acid. In addition, they will be asked to complete food surveys and two sets of 3-day dietary records, and to provide colon biopsies for this study during their routine colonoscopy, as well as a blood, and two urine and stool samples. Urine samples will be used for analysis of urolithin, ellagic acid metabolites. Stool samples will be used to assess gut microbiota changes after walnut consumption. Dietary records will be used for compliance and Food Frequency Questionnaire will be used to assess dietary habits. Lastly, the biopsy samples will be used for analysis of biomarkers and anti-inflammatory in the colon, as well as adherent microbiome to the colonic tissue. Data will be analyzed based on the urolithin phenotypes.

Conditions

Colo-rectal Cancer; Colon Cancer; Diet Habit

Keywords

Colorectal cancer; Microbiome; Urolithins; Walnuts

Outcome Measures

Primary Outcomes (2)

• Leve of Urolithin of this Population

  Urolithin will be measure in urine using a mass spectrometer to characterize this population into three know urolithin phenotypes, Uro-A, Uro-B and Uro-0, after walnut consumption.

  28 days post walnuts

• Urolithin Phenotype and Colonic Health

  Assess biomarkers in colonic mucosa from biopsy samples collected at colonoscopy that are associated with the three different urolithin metabotype following walnut consumption. This biomarkers is a total of 287 genes involved in cellular apoptosis and proliferation, inflammation and senescence, including TIMP1 (used for power calculations), cytokine and T cell and B cell signaling genes, as well as markers of lymphocyte subsets and immune checkpoint pathways and targets, providing a wide range of functional annotation groups.

  28 days post walnuts

Secondary Outcomes (1)

• Identify Changes in Microbiota and Microbes Responsible for Urolithin Formation Followed by Walnuts Consumption using Metagenomics Sequencing

  Day 7 to Day 28

Study Arms (1)

Walnut Consumption

EXPERIMENTAL

After screening, participants will avoid foods high in ellagic acid. These foods include pomegranates, hazelnuts, pistachios, strawberries, raspberries, blackberries, oak-aged wines, spirits, and walnuts (besides the ones given by researchers); a complete list will be provided to the subjects. Participants will then return to research facility and provide urine and stool samples, as well as a set of 3-day dietary records. Then, they will start to consume 2 ounces of walnuts per day for 21 days with their usual diet. At the end, they will collect another urine and stool sample as well as another set of dietary records, and then come in for the scheduled colonoscopy where they will be asked to provide biopsy specimens. That completes the intervention and participation in the study.

Other: Walnuts

Interventions

Walnuts OTHER

Participants will consume 2 ounces of walnuts for 21 days

Walnut Consumption

Eligibility Criteria

• Age: 50 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women between the ages of 50-65 years old who are scheduled to undergo a routine screening colonoscopy
• English speaking/reading patients willing and able to provide written informed consent for study participation
• Patients willing to consume walnuts for 3 weeks
• Willingness to comply with all study requirements

You may not qualify if:

• Current active malignancy, previous history of gastrointestinal malignancy, or altered gastrointestinal anatomy
• Current evidence or previous history of ulcerative colitis or Crohn's disease
• HIV infection, chronic viral hepatitis
• Allergy to walnuts or hypersensitivity to tree nuts
• Use of antibiotics within the past month
• Individuals with blood coagulation disorders or on anti-coagulant therapy
• Treated with steroids, immunosuppressive agents or other anti-inflammatory drugs one week prior to starting intervention
• Non-English-speaking patients who require an interpreter to give consent
• Patients residing in the Department of Correction
• Inability to comply with the protocol requirements
• Any other condition that, in the opinion of the PI, might interfere with study objectives

Sponsors & Collaborators

• UConn Health: lead
• American Institute for Cancer Research: collaborator
• California Walnut Commission: collaborator
• The Jackson Laboratory: collaborator

Study Sites (1)

University of Connecticut Health Center

Farmington, Connecticut, 06030, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Feeding Behavior; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Behavior, Animal; Behavior; Rectal Diseases

Study Officials

• JOHN BIRK, MD

  UConn Health

  STUDY CHAIR

• DANIEL W ROSENBERG, PhD

  UConn Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 20, 2019
• First Posted: August 26, 2019
• Study Start: May 20, 2019
• Primary Completion: April 8, 2021
• Study Completion: April 8, 2021
• Last Updated: November 26, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)