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Cardiovascular DiseaseNCT02210767

Effects of Walnuts on Central Blood Pressure, Arterial Stiffness Indices, Lipoproteins, and Other CVD Risk Factors

A study testing Walnut Diet and Low ALA Diet in people with Cardiovascular Disease, run by Penn State University at 1 site 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

This study will evaluate the effects of walnut-derived ALA and bioactives on multiple CVD risk factors, including central blood pressure, arterial stiffness indices, inflammatory markers, urinary isoprostanes, vascular adhesion markers, and changes in lipids and lipoproteins. Read more about this study

Who is it for?
Ages 30 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Cardiovascular Disease
What is being tested?
Walnut Diet and Low ALA Diet
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
46 participants
Where
1 siteUnited States
Study dates
Aug 2014to Apr 2018
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 30 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Aged 30-65 years
  • BMI greater than 25 and less than or equal to 40 kg/m2
  • Non-smokers
  • TG < 350 mg/dL
  • LDL-C between the 25-95th percentile from NHANES:
  • Males: 105-194 mg/dL
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  • Females: 98-190 mg/dL
  • Stage I hypertension:
  • SBP > 120 mmHg and/or DBP > 80 mmHg
  • SBP < 160 mmHg and DBP < 100 mmHg
  • Free of established CVD, stroke, diabetes, liver, kidney or autoimmune disease.

Who cannot join

  • Elevated BP (SBP ≥160 mmHg OR DBP ≥ 100 mmHg)
  • A history of myocardial infarction, stroke, diabetes mellitus, liver disease, inflammatory disease, kidney disease, and/or thyroid disease (unless controlled on medication).
  • Blood pressure or cholesterol-lowering medication use
  • Refusal to discontinue intake of putative cholesterol-lowering supplements (psyllium, fish oil capsules, soy lecithin, niacin, fiber, flax, and phytoestrogens).
  • Vegetarianism or other dietary practices that are inconsistent with the test diets
  • Nut allergies (Other food allergies will be reviewed on a case-by-case basis)
Show all 9Show fewer
  • Refusal to discontinue nutritional supplements, herbs, vitamins or NSAID's
  • Latex allergy
  • Pregnant or lactating females

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Penn State University

    University Park, Pennsylvania, 16802

Other trials in United States

About this study

This study will evaluate the effects of walnut-derived ALA and bioactives on multiple CVD risk factors, including central blood pressure, arterial stiffness indices, inflammatory markers, urinary isoprostanes, vascular adhesion markers, and changes in lipids and lipoproteins. Gut microbiome changes due to walnut consumption will also be assessed using the 16S rRNA gene.

Read the detailed description

Diets containing nuts likely reduce cardiovascular disease (CVD) risk but the mechanisms remain poorly defined. Walnuts contain substantial amounts of polyunsaturated fatty acids (PUFAs), particularly alpha-linolenic acid (ALA), and are a rich source of bioactives. Many vegetable oils are high in PUFAs but most lack ALA and do not provide the same complement of bioactive compounds as walnuts. ALA is thought to improve cardiovascular health by modulating circulating lipid concentrations, altering membrane structure/function by enhancing the total ω-3 fatty acid content of cell membrane phospholipids, and reducing inflammatory reactions by inhibiting production of arachidonic acid-derived eicosanoids. Consumption of walnuts has consistently been shown to improve blood lipids/lipoproteins and vascular health. However, there remains much debate over what is the preferable replacement for saturated fat in the diet. Because of the ALA and bioactives that they provide, walnuts may confer specific CVD benefits. To study the effects of walnuts, in terms of both their ALA content and bioactive compounds, we will compare two test diets (one containing walnuts and one matched for PUFA and ALA content but devoid of walnuts and their bioactives) to a control diet matched for macronutrient and linoleic acid (LA) content but providing oleic acid in place of ALA. This diet design will provide information about how walnuts affect the selected endpoints of interest due to their bioactives as well as their ALA content, and whether walnut ALA is a superior substitute for dietary saturated fat compared to oleic acid.

Feeding protocol and study treatments:

This study is designed as a double-blind, 3-period, randomized, cross-over controlled feeding study. Prior to randomization, participants will complete a two week run-in on a standard Western diet. Each diet period treatment phase will be 6 weeks in duration, separated by 2-week washout periods. The three test diets are: 1) a walnut diet (WD; providing ~2.0 oz of walnuts per day); 2) a matched walnut control diet (WCD) that will provide the same fatty acid profile as the walnut diet, but will not contain walnuts (and their bioactives); and 3) a low ALA diet (LAD) with a similar macronutrient (and linoleic acid) composition as the WD and WCD, but using oleic acid to replace ALA. Study diets will be prepared in a metabolic kitchen, with three isocaloric meals and a snack provided each day, based on a 7-day rotating menu cycle. Participants will be instructed to consume only the prepared foods and limit their intake of alcohol to 2 drinks/week and caffeinated calorie-free beverages to 40 ounces (5 drinks) per day. Diets will be planned for every subject according to his/her energy requirements and will be nutritionally adequate. This diet design will permit the WD to be compared with the WCD and LAD and, thereby, allow us to ascertain the specific effects that walnuts and their bioactive components (including and beyond ALA) may have on CVD risk factors and artery health.

Being tested
Walnut Diet, Walnut Control Diet, Low ALA Diet
Medical subject headings
Cardiovascular Diseases

What participants receive

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

  • Walnut DietOther

    2 oz. walnuts/day (2-3% of total calories from ALA)

  • Walnut Control DietOther

    2-3% ALA but no walnuts provided

  • Low ALA DietOther

    ALA replaced by oleic acid

Study groups in NCT02210767
Study groupRoleWhat they receive
Walnut DietExperimentalProvides ~2 oz. walnuts/day (2-3% of total calories from alpha-linolenic acid [ALA])
Receives: Other: Walnut Diet
Walnut Control DietActive comparatorProvides same fatty acid profile (<7% SFA, 9% MUFA, 14-15% PUFA, 2-3% ALA) as Walnut Diet, but is devoid of walnuts and their bioactives
Receives: Other: Walnut Control Diet
Low ALA DietPlacebo comparatorProvides similar macronutrient and linoleic acid profile but replaces ALA with oleic acid (<7% SFA, 12% MUFA, 12% PUFA, 0.5% ALA)
Receives: Other: Low ALA Diet

What is being measured

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

  1. Change from baseline in central blood pressure at the end of diet period 1 (week 6), end of diet period 2 (week 14), and end of diet period 3 (week 22)

    Measured: End of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)

Secondary outcomes (12)
  1. Change in 24-hour ambulatory blood pressure

    Measured: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)

  2. Change in indices of arterial stiffness (pulse wave velocity)

    Measured: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)

  3. Change in lipoprotein particle size

    The VAP© Test provides a direct measure of the following lipid and lipoprotein classes and subclasses: LDL, Lp(a), IDL, LDL1, LDL2, LDL3, LDL4, HDL, HDL2, HDL3, VLDL, VLDL1+2, VLDL3, TC, TG, Non-HDL, Remnant Lipoproteins, ApoB100, and ApoA1

    Measured: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)

  4. Change in inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6)

    Measured: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)

  5. Change in the composition of the gut microbiome

    This will be assessed via sequencing of microbial 16S rRNA from fecal samples.

    Measured: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)

  6. Change in serum C-reactive protein

    Measured: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)

  7. Change in serum glucose

    Measured: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)

  8. Change in serum insulin

    Measured: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)

  9. Change in urinary F2α-isoprostanes

    Measured: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)

  10. Change in lipid/lipoprotein profile

    Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides

    Measured: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)

  11. Change in heart rate variability

    Measured: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)

  12. Change in vascular adhesion markers (VCAM and ICAM)

    Measured: Week 0, end of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)

Timeline

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

  1. First posted7 Aug 2014 (estimated)
  2. Study startAug 2014
  3. Primary completionApr 2018
  4. Study completionApr 2018

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
Other
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02210767
Sponsor's protocol ID
PKE ALA
Status last verified
Aug 2023
First submitted
17 Jul 2014
Last updated
21 Aug 2023
Results posted
No
Data monitoring committee
No

Publications

  • McGuire S. U.S. Department of Agriculture and U.S. Department of Health and Human Services, Dietary Guidelines for Americans, 2010. 7th Edition, Washington, DC: U.S. Government Printing Office, January 2011. Adv Nutr. 2011 May;2(3):293-4. doi: 10.3945/an.111.000430. Epub 2011 Apr 30. No abstract available.

    PubMed 22332062
  • Sabate J, Fraser GE, Burke K, Knutsen SF, Bennett H, Lindsted KD. Effects of walnuts on serum lipid levels and blood pressure in normal men. N Engl J Med. 1993 Mar 4;328(9):603-7. doi: 10.1056/NEJM199303043280902.

    PubMed 8357360
  • Zhao G, Etherton TD, Martin KR, West SG, Gillies PJ, Kris-Etherton PM. Dietary alpha-linolenic acid reduces inflammatory and lipid cardiovascular risk factors in hypercholesterolemic men and women. J Nutr. 2004 Nov;134(11):2991-7. doi: 10.1093/jn/134.11.2991.

    PubMed 15514264
  • Banel DK, Hu FB. Effects of walnut consumption on blood lipids and other cardiovascular risk factors: a meta-analysis and systematic review. Am J Clin Nutr. 2009 Jul;90(1):56-63. doi: 10.3945/ajcn.2009.27457. Epub 2009 May 20.

    PubMed 19458020
  • West SG, Krick AL, Klein LC, Zhao G, Wojtowicz TF, McGuiness M, Bagshaw DM, Wagner P, Ceballos RM, Holub BJ, Kris-Etherton PM. Effects of diets high in walnuts and flax oil on hemodynamic responses to stress and vascular endothelial function. J Am Coll Nutr. 2010 Dec;29(6):595-603. doi: 10.1080/07315724.2010.10719898.

    PubMed 21677123
  • Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L,Pintó X, Basora J, Muñoz MA, Sorlí JV, Martínez JA, Martínez-González MA; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368:1279-1290.

  • Zhang J, Grieger JA, Kris-Etherton PM, Thompson JT, Gillies PJ, Fleming JA, Vanden Heuvel JP. Walnut oil increases cholesterol efflux through inhibition of stearoyl CoA desaturase 1 in THP-1 macrophage-derived foam cells. Nutr Metab (Lond). 2011 Aug 26;8:61. doi: 10.1186/1743-7075-8-61.

    PubMed 21871057
  • Petersen KS, Chandra M, Chen See JR, Leister J, Jafari F, Tindall A, Kris-Etherton PM, Lamendella R. Walnut consumption and gut microbial metabolism: Results of an exploratory analysis from a randomized, crossover, controlled-feeding study. Clin Nutr. 2023 Nov;42(11):2258-2269. doi: 10.1016/j.clnu.2023.09.023. Epub 2023 Sep 28.

    PubMed 37826992
  • Tindall AM, McLimans CJ, Petersen KS, Kris-Etherton PM, Lamendella R. Walnuts and Vegetable Oils Containing Oleic Acid Differentially Affect the Gut Microbiota and Associations with Cardiovascular Risk Factors: Follow-up of a Randomized, Controlled, Feeding Trial in Adults at Risk for Cardiovascular Disease. J Nutr. 2020 Apr 1;150(4):806-817. doi: 10.1093/jn/nxz289.

    PubMed 31848609
  • Tindall AM, Petersen KS, Skulas-Ray AC, Richter CK, Proctor DN, Kris-Etherton PM. Replacing Saturated Fat With Walnuts or Vegetable Oils Improves Central Blood Pressure and Serum Lipids in Adults at Risk for Cardiovascular Disease: A Randomized Controlled-Feeding Trial. J Am Heart Assoc. 2019 May 7;8(9):e011512. doi: 10.1161/JAHA.118.011512.

    PubMed 31039663

Questions about this trial

What is this clinical trial studying?

A study testing Walnut Diet and Low ALA Diet in people with Cardiovascular Disease, run by Penn State University 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 11 inclusion and 9 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 21 Aug 2023. 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. Some participants in this study may receive a placebo. 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?

Change from baseline in central blood pressure at the end of diet period 1 (week 6), end of diet period 2 (week 14), and end of diet period 3 (week 22) (time frame: End of diet period 1 (week 6), end of diet period 2 (week 14), end of diet period 3 (week 22)). 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 NCT02210767, which also lists 10 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 21 Aug 2023.

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