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Colorectal CancerNCT05195970

Walnuts and Colon Health (The WellNut Trial)

A study testing Walnuts in people with Colorectal Cancer and Diet Habit, run by UConn Health at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 39 to 75 yearsHealthy volunteers can take part
Conditions the study is for
Colorectal Cancer, Diet Habit
What is being tested?
Walnuts
Could I receive a placebo?
No, everyone receives an active treatment
How many people
140 participants
Where
2 sitesUnited States
Study dates
24 Jan 2022to 30 Jan 2026
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 39 to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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):
  • Individuals who have a family history of colon polyps or CRC in a first-degree relative diagnosed with CRC under the age of 65 years, or
  • 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
  • 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
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  • Willing to avoid intake of EA/ET-rich foods and beverages (e.g., pomegranates, hazelnuts, pistachios, strawberries, raspberries, blackberries, oak-aged wines, and other items 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • UConn Health

    Farmington, Connecticut, 06032

  • Weill Cornell Medicine

    New York, New York, 10065

Other trials in United States

About this study

Official title: Microbiota, Metabolites and Colon Neoplasia

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.

Read the detailed description

This is a 30-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.

Being tested
Walnuts
Keywords
Colorectal cancer, Microbiome, Urolithin, Walnuts, Diet habit, Inflammatory markers, Colon inflammation
Medical subject headings
Colorectal Neoplasms, Feeding Behavior, Colitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • WalnutsOther

    Participants consume 2 ounces of walnuts daily for 21 days

Study groups in NCT05195970
Study groupRoleWhat they receive
Walnut ConsumptionExperimentalFollowing 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.
Receives: Other: Walnuts

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Day 7 and Day 28

  2. 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).

    Measured: Day 7 and Day 28

  3. 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).

    Measured: Day 7 and Day 28

  4. 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 30 (post-walnut supplementation/end of study).

    Measured: Day 0, Day 7 and Day 30

  5. 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 adenomas/polyps (SSA/Ps)) detected during the colonoscopy procedure at the end of the study (day 30).

    Measured: Day 30

  6. 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).

    Measured: Day 7 and Day 28

  7. Correlation of colonic lesion gene expression with urolithin production

    Colonic lesion (AAs and SSA/Ps) biopsies obtained at the end of the study (day 30) 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.

    Measured: Day 30

  8. Association of urolithin levels with the immune composition of the tumor microenvironment

    FFPE colon polyp tissue sections will be analyzed by the NCI Imaging Core (Frederick, MD) using imaging mass cytometry (IMC) to determine immune cell populations present within the tumor microenvironment. This data will be used to establish correlations with urolithin production.

    Measured: Day 30

Secondary outcomes (6)
  1. 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 30 (post-walnut supplementation).

    Measured: Day 7 and Day 30

  2. 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 30 (post-walnut supplementation).

    Measured: Day 7 and Day 30

  3. 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 30 (end of study).

    Measured: Day 7 and Day 30

  4. 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 30).

    Measured: Day 7 and Day 30

  5. 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 30 (post-walnut supplementation).

    Measured: Day 7 and Day 30

  6. 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 30 (post-walnut supplementation).

    Measured: Day 7 and Day 30

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jan 2022
  2. Study start24 Jan 2022
  3. Primary completion30 Jan 2026
  4. Study completion30 Jan 2026

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
140 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05195970
Sponsor's protocol ID
21-167JS-1
Other IDs
1R01CA252045-01A1
Status last verified
Apr 2026
First submitted
24 Nov 2021
Last updated
5 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Fan N, Fusco JL, Rosenberg DW. Antioxidant and Anti-Inflammatory Properties of Walnut Constituents: Focus on Personalized Cancer Prevention and the Microbiome. Antioxidants (Basel). 2023 Apr 22;12(5):982. doi: 10.3390/antiox12050982.

    PubMed 37237848
  • Liu H, Birk JW, Provatas AA, Vaziri H, Fan N, Rosenberg DW, Gharaibeh RZ, Jobin C. Correlation between intestinal microbiota and urolithin metabolism in a human walnut dietary intervention. BMC Microbiol. 2024 Nov 15;24(1):476. doi: 10.1186/s12866-024-03626-5.

    PubMed 39548408
  • Moussa MR, Fan N, Birk J, Provatas AA, Mehta P, Hatano Y, Chun OK, Darooghegi Mofrad M, Lotfi A, Aksenov A, Motta VN, Zenali M, Vaziri H, Grady JJ, Nakanishi M, Rosenberg DW. Systemic Inflammation and the Inflammatory Context of the Colonic Microenvironment Are Improved by Urolithin A. Cancer Prev Res (Phila). 2025 Apr 1;18(4):235-250. doi: 10.1158/1940-6207.CAPR-24-0383.

    PubMed 39995164
  • 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.

    PubMed 31137456
  • 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.

    PubMed 31818852
  • 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.

    PubMed 27215566
  • 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.

    PubMed 31754633
  • 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.

    PubMed 27158799

Questions about this trial

What is this clinical trial studying?

A study testing Walnuts in people with Colorectal Cancer and Diet Habit, run by UConn Health at 2 sites 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 10 inclusion and 13 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 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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?

Bacterial composition and taxonomy changes in the fecal microbiome (time frame: Day 7 and Day 28). The study lists 8 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 NCT05195970, which also lists 8 linked publications.

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 5 Oct 2026.

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