Back to resultsResponse of Gut Microbiota and Cardiometabolic Biomarkers to Consumption of Walnuts
Primary Purpose
Healthy, Normal Weight, Overweight
Status
Withdrawn
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Walnut
Nut-Free
Sponsored by
About this trial
This is an interventional basic science trial for Healthy
Eligibility Criteria
Inclusion Criteria:
Generally healthy men and women between 20-65 years of age and BMI range of 20.0-34.9 kg/m2 will be recruited from the Davis - Sacramento metropolitan area. Enrolled subjects must be willing to consume 2 ounces (approximately 1/2 cup) of walnuts daily and modify their diet to avoid eating walnuts and other nuts, and foods or beverages high in polyphenols (a list will be provided) during study enrollment . Adults unable to consent, individuals who are not yet adults (infants, children, teenagers), pregnant or lactating women, women planning to become pregnant in the next four months and prisoners will be specifically excluded. Screening will take place by phone interview and through in-person screening and consent, including anthropometric and biochemical assessments and health history questionnaires.
Exclusion Criteria:
- Allergy to walnuts or other nuts
- Eating more than 25 grams of fiber per day, assessed by the Block Dietary-Fruit-Vegetable-Fiber Screener©
- Taking medications or supplements known to affect metabolism or gut microbiota composition (i.e. Metformin, statins, antibiotics within the past 3 months, fiber supplements, probiotics, and others)
- Documented chronic diseases including diabetes, renal or liver disease, metabolic syndrome, active cancer, MI or stroke, history of gastric bypass or GI disease (e.g. Crohn's Disease, Irritable Bowel Disease, diverticulosis/diverticulitis,etc)
- Smoker or living with a smoker, including vaporizer and/or electronic cigarettes.
- Illicit drug use, cannabis usage, or consuming >1 alcoholic drink/day
- Extreme dietary or exercise patterns; vegan diet.
- Recent weight fluctuations (>10% in the last 6 months)
- Taking prescription lipid medications or supplements that may affect lipoprotein metabolism (i.e. >1 g of fish oil/day, antioxidant supplements)
- Taking exogenous hormones (e.g. hormonal birth control)
- Poor venous access
- Unwillingness to comply with study protocols
Sites / Locations
- Ragle Human Nutrition Research Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Walnut
Nut-Free
Arm Description
Eat 2 ounces of walnuts provided by the study. Eating any other nuts is to be avoided. Background diet will be low in polyphenols.
Eating any other nuts is to be avoided. Background diet will be low in polyphenols.
Outcomes
Primary Outcome Measures
Assessing the influence of walnuts on the fecal metagenome
Changes in fecal metagenomics will be assessed via Illumina sequencing
Assessing the influence of walnuts on fecal secondary bile acids
Fecal secondary bile acids will be measured by LC-QTOF/MS
Assessing the influence of walnuts on fecal short-chain fatty acids
Short-chain fatty acids in fecal matter will be measured by LC-MS/MS
Urolithins measured in plasma by UPLC/MS
Measure for changes in the levels of urolithins in separated plasma; measured in units of ug/uL. Blood will be assessed at each of the 4 study visits.
Fecal calprotectin will be measured by ELISA
Measure for changes in the levels of calprotectin in collected fecal matter; measured in units of ug/g. Feces will be assessed at each of the 4 study visits.
Secondary Outcome Measures
Assessing the influence of walnuts on blood lipid measurements
Measure for changes in the levels of HDL and LDL in separated plasma; measured in units of mg/dL. Blood will be assessed at each of the 4 study visits
Assessing the influence of walnuts on paraoxonase-1 (PON-1) activity
Measure for changes in PON-1 activity in separated plasma at each study of the 4 study visits. Activity will be calculated based on linear rates of hydrolysis of phenyl acetate to phenol
Assessing the influence of walnuts on cholesterol ester transfer protein activity (CETP)
Changes in CETP activity will be measured at each of the 4 study visits. The isolated plasma will be co-incubated with donor and acceptor molecules using a commercially available assay kit.
Assessing the influence of walnuts on hsCRP will be measured in blood
hsCRP will be measured in blood at each study visit
Assessing the influence of walnuts on SAA will be measured in blood
SAA will be measured in blood at each study visit
Assessing the influence of walnuts on circulating cytokines
ICAM and VCAM will be measured in blood at each study visit using a commercially available ELISA kit.
Assessing the influence of walnuts on peripheral blood mononuclear cells (PBMC) using ex vivo stimulation assays
In-vitro: media from LPS stimulated monocytes will be used to measure gene expression and cytokines Measurement of changes in PBMC derived cytokines as a marker of inflammation at each of the 4 study visits. Assessment will be based on an increase or decrease in concentration in pg/ml.
Dietary record analysis
Use a computer program to check for study dietary requirements. Subjects are to avoid olives and olive containing products during study protocol periods. This will be done using a subject self-recorded 3-day food record submitted to study personnel.
Anthropometric measurements
Measure waist (cm) and hip circumference (cm) before the start of drawing blood on study day protocols.
Measure for changes in weight
Measure weight (kg) before the start of drawing blood on study day protocols
Measure for changes in blood pressure
Measure blood pressure (mmHg) before the start of drawing blood on study day protocols
Full Information
NCT ID
NCT04307628
First Posted
March 10, 2020
Last Updated
September 14, 2023
Sponsor
University of California, Davis
1. Study Identification
Unique Protocol Identification Number
NCT04307628
Brief Title
Response of Gut Microbiota and Cardiometabolic Biomarkers to Consumption of Walnuts
Official Title
Response of Gut Microbiota and Cardiometabolic Biomarkers to Consumption of Walnuts
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Study logistics still being worked out. On hold for now.
Study Start Date
June 1, 2022 (Anticipated)
Primary Completion Date
March 31, 2024 (Anticipated)
Study Completion Date
November 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, Davis
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The researchers will investigate blood and fecal responses in qualified study participants after eating walnuts for 4 weeks compared to not eating walnuts for 4 weeks. The two dietary interventions will be separated by a 4 week washout period. The order of diets will be random; study participants will complete both interventions. Dietary modifications will be part of the study protocol.
Detailed Description
The researchers hypothesize that walnut consumption will induce changes in fecal metagenome, identifiable walnut-derived bioactives (urolithins) and other microbial-derived products (short-chain fatty acids and secondary bile acids). The researchers hypothesize that walnut consumption will result in improvements to blood lipid profiles, including decreased total and LDL-cholesterol; increased HDL-related cholesterol efflux capacity and antioxidant protection; and decreased inflammatory biomarkers relative to control diet. The researchers hypothesize changes in cardiometabolic health biomarkers will be correlated with food bioactive metabolites and/or fecal metagenome. Pathway analysis will identify metabolic pathways differentially regulated by walnut-derived bioactives and walnut-responsive microbial genes.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy, Normal Weight, Overweight, Obese
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Walnut
Arm Type
Active Comparator
Arm Description
Eat 2 ounces of walnuts provided by the study. Eating any other nuts is to be avoided. Background diet will be low in polyphenols.
Arm Title
Nut-Free
Arm Type
Placebo Comparator
Arm Description
Eating any other nuts is to be avoided. Background diet will be low in polyphenols.
Intervention Type
Other
Intervention Name(s)
Walnut
Intervention Description
Study participants will eat 2 ounces of walnuts each day.
Intervention Type
Other
Intervention Name(s)
Nut-Free
Intervention Description
Study participants will not eat nuts.
Primary Outcome Measure Information:
Title
Assessing the influence of walnuts on the fecal metagenome
Description
Changes in fecal metagenomics will be assessed via Illumina sequencing
Time Frame
Through study completion, an average of 12 weeks
Title
Assessing the influence of walnuts on fecal secondary bile acids
Description
Fecal secondary bile acids will be measured by LC-QTOF/MS
Time Frame
Through study completion, an average of 12 weeks
Title
Assessing the influence of walnuts on fecal short-chain fatty acids
Description
Short-chain fatty acids in fecal matter will be measured by LC-MS/MS
Time Frame
Through study completion, an average of 12 weeks
Title
Urolithins measured in plasma by UPLC/MS
Description
Measure for changes in the levels of urolithins in separated plasma; measured in units of ug/uL. Blood will be assessed at each of the 4 study visits.
Time Frame
Through study completion, an average of 12 weeks
Title
Fecal calprotectin will be measured by ELISA
Description
Measure for changes in the levels of calprotectin in collected fecal matter; measured in units of ug/g. Feces will be assessed at each of the 4 study visits.
Time Frame
Through study completion, an average of 12 weeks
Secondary Outcome Measure Information:
Title
Assessing the influence of walnuts on blood lipid measurements
Description
Measure for changes in the levels of HDL and LDL in separated plasma; measured in units of mg/dL. Blood will be assessed at each of the 4 study visits
Time Frame
Through study completion, an average of 12 weeks
Title
Assessing the influence of walnuts on paraoxonase-1 (PON-1) activity
Description
Measure for changes in PON-1 activity in separated plasma at each study of the 4 study visits. Activity will be calculated based on linear rates of hydrolysis of phenyl acetate to phenol
Time Frame
Through study completion, an average of 12 weeks
Title
Assessing the influence of walnuts on cholesterol ester transfer protein activity (CETP)
Description
Changes in CETP activity will be measured at each of the 4 study visits. The isolated plasma will be co-incubated with donor and acceptor molecules using a commercially available assay kit.
Time Frame
Through study completion, an average of 12 weeks
Title
Assessing the influence of walnuts on hsCRP will be measured in blood
Description
hsCRP will be measured in blood at each study visit
Time Frame
Through study completion, an average of 12 weeks
Title
Assessing the influence of walnuts on SAA will be measured in blood
Description
SAA will be measured in blood at each study visit
Time Frame
Through study completion, an average of 12 weeks
Title
Assessing the influence of walnuts on circulating cytokines
Description
ICAM and VCAM will be measured in blood at each study visit using a commercially available ELISA kit.
Time Frame
Through study completion, an average of 12 weeks
Title
Assessing the influence of walnuts on peripheral blood mononuclear cells (PBMC) using ex vivo stimulation assays
Description
In-vitro: media from LPS stimulated monocytes will be used to measure gene expression and cytokines Measurement of changes in PBMC derived cytokines as a marker of inflammation at each of the 4 study visits. Assessment will be based on an increase or decrease in concentration in pg/ml.
Time Frame
Through study completion, an average of 12 weeks
Title
Dietary record analysis
Description
Use a computer program to check for study dietary requirements. Subjects are to avoid olives and olive containing products during study protocol periods. This will be done using a subject self-recorded 3-day food record submitted to study personnel.
Time Frame
Through study completion, an average of 12 weeks
Title
Anthropometric measurements
Description
Measure waist (cm) and hip circumference (cm) before the start of drawing blood on study day protocols.
Time Frame
Through study completion, an average of 12 weeks
Title
Measure for changes in weight
Description
Measure weight (kg) before the start of drawing blood on study day protocols
Time Frame
Through study completion, an average of 12 weeks
Title
Measure for changes in blood pressure
Description
Measure blood pressure (mmHg) before the start of drawing blood on study day protocols
Time Frame
Through study completion, an average of 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Generally healthy men and women between 20-65 years of age and BMI range of 20.0-34.9 kg/m2 will be recruited from the Davis - Sacramento metropolitan area. Enrolled subjects must be willing to consume 2 ounces (approximately 1/2 cup) of walnuts daily and modify their diet to avoid eating walnuts and other nuts, and foods or beverages high in polyphenols (a list will be provided) during study enrollment . Adults unable to consent, individuals who are not yet adults (infants, children, teenagers), pregnant or lactating women, women planning to become pregnant in the next four months and prisoners will be specifically excluded. Screening will take place by phone interview and through in-person screening and consent, including anthropometric and biochemical assessments and health history questionnaires.
Exclusion Criteria:
Allergy to walnuts or other nuts
Eating more than 25 grams of fiber per day, assessed by the Block Dietary-Fruit-Vegetable-Fiber Screener©
Taking medications or supplements known to affect metabolism or gut microbiota composition (i.e. Metformin, statins, antibiotics within the past 3 months, fiber supplements, probiotics, and others)
Documented chronic diseases including diabetes, renal or liver disease, metabolic syndrome, active cancer, MI or stroke, history of gastric bypass or GI disease (e.g. Crohn's Disease, Irritable Bowel Disease, diverticulosis/diverticulitis,etc)
Smoker or living with a smoker, including vaporizer and/or electronic cigarettes.
Illicit drug use, cannabis usage, or consuming >1 alcoholic drink/day
Extreme dietary or exercise patterns; vegan diet.
Recent weight fluctuations (>10% in the last 6 months)
Taking prescription lipid medications or supplements that may affect lipoprotein metabolism (i.e. >1 g of fish oil/day, antioxidant supplements)
Taking exogenous hormones (e.g. hormonal birth control)
Poor venous access
Unwillingness to comply with study protocols
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francene M Steinberg, PhD, RD
Organizational Affiliation
University of California, Davis
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ragle Human Nutrition Research Center
City
Davis
State/Province
California
ZIP/Postal Code
95616
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Response of Gut Microbiota and Cardiometabolic Biomarkers to Consumption of Walnuts
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