Colo-rectal CancerNCT04066816
Ellagic Acid, Urolithin and Colonic Microbial Communities Affected by Walnut Consumption
A study testing Walnuts in people with Colo-rectal Cancer and Colon Cancer, run by UConn Health at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Colo-rectal Cancer, Colon Cancer, Diet Habit
- What is being tested?
- Walnuts
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteUnited States
- Study dates
- 20 May 2019to 8 Apr 2021
- 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 50 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Connecticut Health Center
Farmington, Connecticut, 06030
About this study
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.
Read the detailed description
The investigators propose to address the influence of ellagic acid obtained from walnuts and its microbial-derived metabolites (urolithin) on the gut microbiome and inflammation-related biomarkers in a human clinical study. Patients will be enrolled and detailed demographic and dietary information, biopsy specimens through colonoscopies, as well as fecal, blood and urine samples will be collected. The wide range of gut urolithin levels provides the rationale for our proposed studies. Will the specific urolithin phenotypes show a disparate range of chemopreventive (anti-inflammatory) response to walnut consumption? The hypothesis is that walnut ingestion in "Phenotype A" participants (producing the highest levels of urolithin) will be associated with a beneficial anti-inflammatory response as tested in colonic mucosa and a higher abundance of bacterial species associated with ellagic acid metabolism. Although 16S ribosomal ribonucleic acid gene (rRNA) sequencing allows inexpensive bacterial identification at the genus/species level, a whole genome sequencing (mWGS) will be employed to achieve finer classification (strain level), and identify other microbes (e.g., viruses, fungi, small eukaryotes). Furthermore, mWGS targets the entire genome of each microbe (not just the 16S rRNA gene), allowing for construction of a microbial gene catalogue, including a metabolic pathway description for each sample. This will characterize the functional potential of the microbial community. Ultimately, the proposed studies will inform the application of prebiotic to enhance the formation of urolithin metabolites from ellagic acid for the prevention of inflammation-associated Colorectal Cancer, a development that would have significant translational implications.
- Conditions
- Colo-rectal Cancer, Colon Cancer, Diet Habit
- Being tested
- Walnuts
- Keywords
- Colorectal cancer, Microbiome, Urolithins, Walnuts
- Medical subject headings
- Colonic Neoplasms, Feeding Behavior, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WalnutsOther
Participants will consume 2 ounces of walnuts for 21 days
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Walnuts |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 28 days post walnuts
Secondary outcomes (1)
Identify Changes in Microbiota and Microbes Responsible for Urolithin Formation Followed by Walnuts Consumption using Metagenomics Sequencing
Microbiome will be analyzed before and after walnut consumption with the goal to identify microbes responsible for urolithins production. DNA will be extracted from fecal samples and the V1-3 hyper-variable region of bacterial 16S rRNA genes will be sequenced to analyze bacterial community structure. Although 16S rRNA gene sequencing allows inexpensive bacterial identification to the genus/species level, mWGS will be employed in order to achieve finer classification (strain level), and identify other microbes, including viruses, fungi and small eukaryotes.
Measured: Day 7 to Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2019
- Study start20 May 2019
- Primary completion8 Apr 2021
- Study completion8 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colo-rectal CancerStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- UConn Health
- Sponsor type
- University, hospital or other
- Collaborators
- American Institute for Cancer Research, California Walnut Commission, The Jackson Laboratory
- Responsible party
- Principal investigator, Daniel Rosenberg, UConn Health
- Investigators
- JOHN BIRK, MD, Study chair, UConn HealthDANIEL W ROSENBERG, PhD, Principal investigator, UConn Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04066816
- Sponsor's protocol ID
- 19-121JS-1
- Status last verified
- Nov 2021
- First submitted
- 20 Aug 2019
- Last updated
- 26 Nov 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ellagic Acid, Urolithin and Colonic Microbial Communities Affected by Walnut Consumption
- ClinicalTrials.gov ID
- NCT04066816
- Acronym / sponsor ID
- 19-121JS-1
- Conditions
- Colo-rectal Cancer, Colon Cancer, Diet Habit
- Keywords
- Colorectal cancer, Microbiome, Urolithins, Walnuts
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- UConn HealthUniversity, hospital or other
- Collaborators
- American Institute for Cancer Research, California Walnut Commission, The Jackson Laboratory
- Study start
- 20 May 2019 (actual)
- Primary completion
- 8 Apr 2021 (actual)
- Study completion
- 8 Apr 2021 (actual)
- First posted
- 26 Aug 2019 (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.
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.
Detailed description
The investigators propose to address the influence of ellagic acid obtained from walnuts and its microbial-derived metabolites (urolithin) on the gut microbiome and inflammation-related biomarkers in a human clinical study. Patients will be enrolled and detailed demographic and dietary information, biopsy specimens through colonoscopies, as well as fecal, blood and urine samples will be collected. The wide range of gut urolithin levels provides the rationale for our proposed studies. Will the specific urolithin phenotypes show a disparate range of chemopreventive (anti-inflammatory) response to walnut consumption? The hypothesis is that walnut ingestion in "Phenotype A" participants (producing the highest levels of urolithin) will be associated with a beneficial anti-inflammatory response as tested in colonic mucosa and a higher abundance of bacterial species associated with ellagic acid metabolism. Although 16S ribosomal ribonucleic acid gene (rRNA) sequencing allows inexpensive bacterial identification at the genus/species level, a whole genome sequencing (mWGS) will be employed to achieve finer classification (strain level), and identify other microbes (e.g., viruses, fungi, small eukaryotes). Furthermore, mWGS targets the entire genome of each microbe (not just the 16S rRNA gene), allowing for construction of a microbial gene catalogue, including a metabolic pathway description for each sample. This will characterize the functional potential of the microbial community. Ultimately, the proposed studies will inform the application of prebiotic to enhance the formation of urolithin metabolites from ellagic acid for the prevention of inflammation-associated Colorectal Cancer, a development that would have significant translational implications.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Walnut Consumption | Experimental | Other: WalnutsAfter 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. |
Who may qualify
- Ages
- 50 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (11 listed)
- 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
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 |
|---|---|---|
| WalnutsParticipants will consume 2 ounces of walnuts for 21 days | Other | Walnut Consumption |
Primary outcome
Leve of Urolithin of this Population
Time frame: 28 days post walnuts
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.
Urolithin Phenotype and Colonic Health
Time frame: 28 days post walnuts
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.
1 secondary outcome
Identify Changes in Microbiota and Microbes Responsible for Urolithin Formation Followed by Walnuts Consumption using Metagenomics Sequencing
Time frame: Day 7 to Day 28
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 26 Nov 2021.
- Individual participant dataSharing planned: No
Related trials for Colo-rectal Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
Not yet recruitingPhase 2
Alberta Cancer Exercise Dose in Colorectal Cancer
Cancer, Colorectal Cancer
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.
JOHN BIRK, MD study chair
UConn Health
DANIEL W ROSENBERG, PhD principal investigator
UConn Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Walnuts in people with Colo-rectal Cancer and Colon Cancer, run by UConn Health 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 4 inclusion and 11 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 26 Nov 2021. 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?
Leve of Urolithin of this Population (time frame: 28 days post walnuts). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Nov 2021.