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Influence of Walnut Intake on Vascular Function and Metabolism

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03900403
Recruitment Status : Recruiting
First Posted : April 3, 2019
Last Update Posted : October 21, 2019
Sponsor:
Information provided by (Responsible Party):
University of California, Davis

Brief Summary:
This study seeks to confirm and extend previous finding that four weeks of daily intake of 40 g of walnuts improve microvascular function, increasing the reactive hyperemia index (RHI), effects which were greatest in individuals with the worst initial RHI and correlating to circulating levels of vasoactive plasma epoxides. The current trial will enroll postmenopausal women who are at risk for cardiovascular disease due to their menopausal status and increased central adiposity. The initial trial focused on non-esterified (i.e. plasma) derived oxylipins, but substantial and unique changes were also observed in the esterified lipoprotein pool. The current study will add the esterified lipoprotein pool, important, as the mechanisms by which walnut intake influences endothelial function are currently undefined, but may include lipoprotein induced modulation of vascular hemostasis. As a secondary objective, primary metabolism and urolithin metabotype will be analyzed as a way to capture the influence of potential differences in habitual diet and metabolism on physiologic response. Therefore, this study will combine measures of cardiovascular physiology, metabolomics, and walnut-derived metabolite analyses to assess the 12 week influence of 40 g of daily walnut intake on the health of overweight and obese postmenopausal women.

Condition or disease Intervention/treatment Phase
Overweight and Obesity Endothelial Dysfunction Cardiovascular Risk Factor Other: Walnut Intake Not Applicable

Detailed Description:

A dietary intervention trial will be conducted to achieve the following objectives and outcomes:

Objective 1: Determine the 12 week change in bioactive lipid mediators, and their relationship to vascular function and platelet reactivity in overweight or obese postmenopausal women with walnut incorporation into their habitual diet.

Objective 2: Assess the contribution of metabolic phenotype on the variance in biomarker response that includes both primary metabolism and urolithin metabotype.

Expected Outcomes: Forty g of daily walnut intake for six- and 12- weeks is predicted to positively impact the production of bioactive lipid mediators known to favorably regulate cardiovascular and inflammatory signaling. AA derived oxylipins produced from COX, LOX, and CYP epoxygenases are known as regulators of inflammation, platelet activation and vascular function. Therefore, understanding how certain foods such as walnuts can change the relative ratio of PUFA substrates (i.e., AA, ALA, LA, EPA and DHA), and their subsequent bioactive species produced through these enzyme pathways is necessary for the refinement of dietary recommendations with regard to specific foods and dietary patterns aimed at reducing the risk of chronic disease. Although a positive outcome is predicted, there may be substantial variability in response. To explore potential genetic and dietary factors that may contribute to the variability in response to the above functional markers, primary metabolism and urolithin metabotype will be assessed.

Objective 3: Assess the influence of 12 weeks of walnut intake on facial wrinkles in postmenopausal women.

Expected Outcome: Tweleve weeks of 40 g of walnut intake will improve facial wrinkles and erythema in the study population, and the improvements will be related to changes in metabotype.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: Open-arm study, comparing the effects of 12 weeks of 40g of walnut intake to 6 weeks of the study participant's habitual diet.
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: The Influence of Daily Walnut Intake on Vascular Function and Associated Changes in Lipid Mediators and Primary Metabolites.
Actual Study Start Date : September 1, 2019
Estimated Primary Completion Date : December 30, 2020
Estimated Study Completion Date : February 28, 2021

Arm Intervention/treatment
No Intervention: Habitual Intake
This will be the comparative arm, of 6 weeks before and after the study participant is on their habitual diet
Experimental: Walnut Intake
Experimental Arm of 12 weeks of Walnut Intake, with study visits at baseline (prior to walnut intake) and after 6 and 12 weeks of 40g of Walnut Intake.
Other: Walnut Intake
40g of daily walnut intake for 12 weeks




Primary Outcome Measures :
  1. Reactive Hyperemia Index (RHI) [ Time Frame: 18 weeks ]
    Digital microvascular function as measured by the EndoPAT2000

  2. Framingham Reactive Hyperemia Index (fRHI) [ Time Frame: 18 weeks ]
    Digital microvascular function as measured by the EndoPAT2000


Secondary Outcome Measures :
  1. Collagen-Induced Platelet Aggregation [ Time Frame: 18 weeks ]
    Optical platelet aggregometry

  2. ADP-Induced Platelet Aggregation [ Time Frame: 18 weeks ]
    Optical platelet aggregometry

  3. Plasma Fatty Acids [ Time Frame: 18 weeks ]
    Circulating levels of non-esterified fatty acids

  4. Plasma Oxylipins [ Time Frame: 18 weeks ]
    Circulating levels of non-esterified oxylipins

  5. Esterified Oxylipins [ Time Frame: 18 weeks ]
    Lipoprotein esterified oxylipins

  6. Esterified Fatty Acids [ Time Frame: 18 weeks ]
    Lipoprotein esterified fatty acids

  7. Urolithin Metabolites [ Time Frame: 18 weeks ]
    Conjugated and unconjugated urolithins

  8. Ellagitannin Metabolites [ Time Frame: 18 weeks ]
    Conjugated and unconjugated Ellagitanin-derived metabolites

  9. Total Nitrate and Nitrite [ Time Frame: 18 weeks ]
    Total nitrate derived from the diet

  10. Nitric Oxide metabolites (RNOX) [ Time Frame: 18 weeks ]
    Nitric oxide metabolites produced from the intervention


Other Outcome Measures:
  1. Blood Pressure [ Time Frame: 18 weeks ]
    Office blood pressure

  2. Complete Metabolic Panel [ Time Frame: 18 weeks ]
    Will include liver enzymes and glucose

  3. Complete Blood Cell Count [ Time Frame: 18 weeks ]
    w Will include total platelet number and mean platelet volume

  4. Lipid Panel [ Time Frame: 18 weeks ]
    Will assess fasting cholesterol and triglyceride levels

  5. Skin Health [ Time Frame: 18 weeks ]
    Will assess fine facial wrinkles and redness



Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Postmenopausal female: 45-65 years
  • Women: lack of menses for at least two years.
  • Subject is willing and able to comply with the study protocols.
  • Subject is willing to participate in all study procedures
  • BMI 25.0 - 35 kg/m2

Exclusion Criteria:

  • BMI ≥ 35 kg/m2
  • Visit 1 Reactive Hyperemia Index (RHI; EndoPAT 2000) ≥ 2.4
  • Dislike or allergy for walnuts or walnut products
  • Self-reported use of daily anticoagulation agents including aspirin, NSAIDs
  • Vegan, Vegetarians, food faddists or those consuming a non-traditional diet
  • Fruit consumption ≥ 3 cups/day
  • Regular consumption of nuts (2-3 servings/week)
  • Vegetable consumption ≥ 4 cups/day for females
  • Coffee/tea ≥ 3 cups/day
  • Dark chocolate ≥ 3 oz/day
  • Self-reported restriction of physical activity due to a chronic health condition
  • Self-reported chronic/routine high intensity exercise
  • Self-reported diabetes
  • Blood pressure ≥ 140/90 mm Hg
  • Self-reported renal or liver disease
  • Self-reported heart disease, which includes cardiovascular events and stroke
  • Peripheral artery disease, Raynaud's syndrome or disease
  • Inability to properly place or wear the PAT probes or abnormal measurements on pre-screening PAT
  • Abnormal Metabolic or CBC panels (laboratory values outside the reference range) if determined to be clinically significant by the study physician.
  • Self-reported cancer within past 5 years
  • Self-reported malabsorption
  • Currently taking prescription drugs or supplements.
  • Supplement use other than a general formula of vitamins and minerals that meet the RDA
  • Not willing to stop any supplement use, including herbal, plant or botanical, fish oil, oil supplements a month prior to study enrollment.
  • Indications of substance or alcohol abuse within the last 3 years
  • Cannabis use
  • Screening LDL ≥ 190 mg/dl for those who have 0-1 major risk factors apart from LDL cholesterol (i.e. family history of premature coronary artery disease (male first degree relative < 55 years; CHD in female first degree relative < 65 years), cigarette smoker, HDL-C ≤ 40 mg/dL]. (using NCEP calculator http://cvdrisk.nhlbi.nih.gov/calculator.asp)
  • Screening LDL ≥ 160 mg/dl for those who have 2 major risk factors apart from LDL cholesterol [i.e. family history of premature coronary artery disease (male first degree relative < 55 years; CHD in female first degree relative < 65 years), cigarette smoker, HDL-C ≤ 40 mg/dL]. (using NCEP calculator http://cvdrisk.nhlbi.nih.gov/calculator.asp);
  • Screening LDL ≥ 130 mg/dl for those who have 2 major risk factors apart from LDL cholesterol [i.e. family history of premature coronary artery disease (male first degree relative < 55 years; CHD in female first degree relative < 65 years), cigarette smoker, HDL-C ≤ 40 mg/dL], and a Framingham 10-year Risk Score 10-20% (using NCEP calculator http://cvdrisk.nhlbi.nih.gov/calculator.asp).
  • Current enrollee in a clinical research study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03900403


Contacts
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Contact: Roberta R Holt, PhD 530-752-4950 rrholt@ucdavis.edu
Contact: Carl L Keen, PhD 530-752-6331 clkeen@ucdavis.edu

Locations
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United States, California
Department of Nutrition Recruiting
Davis, California, United States, 95616
Contact: Roberta R Holt, PhD    530-752-4950    rrholt@ucdavis.edu   
Sponsors and Collaborators
University of California, Davis
Investigators
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Principal Investigator: Roberta R Holt, PhD University of California, Davis

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Responsible Party: University of California, Davis
ClinicalTrials.gov Identifier: NCT03900403    
Other Study ID Numbers: 1313232
First Posted: April 3, 2019    Key Record Dates
Last Update Posted: October 21, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Overweight
Body Weight
Signs and Symptoms