Dietary Prevention of Heart Failure in Hypertensive Metabolic Syndrome

August 20, 2025 updated by: VA Office of Research and Development
Tens of thousands of Veterans have heart failure with preserved ejection fraction (HFpEF), and suffer poor quality of life, frequent hospitalizations, and high death rates. Older Veterans and those with high blood pressure, obesity, and the metabolic syndrome (abnormal cholesterol and resistance to insulin's effects) are particularly at risk for HFpEF. However, it is not clear why only some Veterans in this risk group eventually develop HFpEF. Extensive information from experimental animal models and some human studies suggests that dietary patterns in vulnerable 'salt-sensitive' people could contribute to the risk for HFpEF. Reducing salt intake and increasing overall dietary quality in at-risk Veterans could prevent heart and blood vessel damage that ultimately leads to HFpEF. Reducing the development of HFpEF, which currently has no definitive treatment, is highly relevant to the VA's mission to emphasize prevention of disease and population health.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

COVID-19 in-person visit hold has been removed- screening and actively enrolling. We are not currently performing sublingual darkfield microscopy because of the need for close face-to-face contact with an open-mouthed patient for several minutes in the setting of COVID-19 pandemic.

Patients with heart failure (HF) account for over 1,200,000 VA outpatient visits per year, and HF remains the most common cause for hospital admission in the VA. Approximately 1/3 of Veterans with HF have 'preserved' ejection fraction (HFpEF), or relatively normal contractile function of the heart; such patients suffer functional decline and poor quality of life, and half die within 5 years after diagnosis. Risk factors for developing HFpEF are more common in Veterans than the general population, and the burden of HFpEF to the VA system will rise in the years ahead as these Veterans age. Preventive efforts are critical, but are hampered by gaps in knowledge related to HFpEF pathophysiology. The long term goal of this proposal is to prevent the onset of HFpEF in at-risk Veterans. Hypertension (HTN) confers the highest population-attributable risk for HFpEF, particularly when accompanied by the metabolic syndrome, a constellation of obesity, insulin resistance, and dyslipidemia. Animal models of HTN and metabolic syndrome develop HFpEF due to microvascular oxidative stress and inflammation induced by high sodium intake. Recent data from cardiac biopsies confirm similar mechanisms in human HFpEF. Dietary sodium restriction is widely recommended to prevent HTN-associated heart disease in humans, but this advice is now controversial. Few studies have examined how individual differences in response to sodium intake affect risk. "Salt-sensitive" persons have blood pressure (BP) that changes in parallel with sodium intake, and commonly develop cardiovascular abnormalities associated with HFpEF. The overall objective of this proposal is to evaluate salt-sensitivity as a novel, diet-responsive risk factor for incident HFpEF in Veterans with HTN and metabolic syndrome. The central hypothesis is that the sodium-restricted Dietary Approaches to Stop Hypertension (DASH/SRD) eating pattern will improve cardiovascular functional and structural risk factors for HFpEF in Veterans with the salt-sensitive phenotype. Guided by findings in experimental models, cohort studies, and strong preliminary evidence from the investigators' research group, this hypothesis will be tested in a two-phase study and by pursuing three specific aims: 1) Determine effects of DASH/SRD on functional and structural cardiovascular HFpEF risk factors in salt-sensitive vs. salt-resistant Veterans, 2) measure the effect of an electronically-delivered tailored-messaging intervention on DASH/SRD adherence, and 3) determine effects of DASH/SRD intervention and adoption on microvascular function and assess the endothelial glycocalyx as a biomarker of cardiovascular response to DASH/SRD. Phase 1 of the study is a sequential comparison of DASH/SRD vs. control diet for two weeks each, and Phase 2 a 6-month extension to promote DASH/SRD adherence. The salt-sensitive phenotype will be defined by between-diet changes in 24-hour mean BP during Phase 1. In Phase 2, the efficacy of motivational interviewing-based counseling and the Women's and Men's Hypertension Experiences and Emerging Lifestyles Intervention (WHEELS-I), a tailored messaging program, to sustain DASH/SRD adherence, will be compared. Echocardiography and arterial tonometry will be used to assess HFpEF-related cardiovascular parameters during short- and longer-term dietary modification and their interaction with salt-sensitivity. In vivo microscopy and novel blood testing will assess microvascular function and the integrity of the endothelial glycocalyx, a blood vessel lining that is sodium-responsive and may mediate the adverse effects of salt-sensitivity. This proposal is innovative because it represents the first study to examine salt-sensitivity as a factor promoting HFpEF in Veterans with HTN and metabolic syndrome, the highest risk group for incident HFpEF. Moreover, it aims to link microvascular dysfunction, an important pathway in human HFpEF, with endothelial glycocalyx damage, a potential biomarker for sodium-mediated vascular risk. The proposed research is significant because it will vertically advance the investigators' understanding of how dietary factors contribute to the pathophysiology of HFpEF, a major and growing health threat to Veterans.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
71

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48105-2303
        • VA Ann Arbor Healthcare System, Ann Arbor, MI

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

45 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Veterans aged 45 years with HTN

    • here defined as screening systolic BP 130 and/or diastolic BP 85 mmHg, or current use of anti-hypertensive drugs

  • and metabolic syndrome

    • body mass index 30 kg/m2 and/or waist circumference >94 cm
  • Participants must also be willing to participate in the WHEELS-I program by using a smartphone application or email

Exclusion Criteria:

  • On-treatment systolic BP of >160 mmHg at screening visit
  • previous history of HF
  • left ventricular ejection fraction <50%
  • moderate or severe valvular heart disease
  • myocardial infarction or stroke within the prior 6 months
  • chronic kidney disease with estimated glomerular filtration rate <45 ml/min/ 1.73m2
  • unoperated aortic aneurysm for which surgery is indicated, prior hyperkalemia requiring urgent treatment
  • hemoglobin <9 gm/dL

  • investigator-determined factors: severe pulmonary disease, e.g.:

    • oxygen-requiring

  • hepatic disease, e.g.:

    • cirrhosis
  • severely uncontrolled diabetes (hemoglobin A1c >10%)
  • active cancer other than non-melanoma skin or low-risk prostate cancer
  • other comorbidity with expected survival <12 months
  • active alcohol/illicit substance abuse
  • and/or a history of persistent nonadherence to treatment
  • Veterans involved in another study (unless it is survey-only and the other investigator will allow us to invite the person in a survey-only study to consider our study)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Motivational Interviewing + WHEELS-I
In addition to motivational interviewing-based counseling with a registered dietitian to promote adoption of the sodium-restricted Dietary Approaches to Stop Hypertension (DASH/SRD) eating plan., participants in this arm will also receive an electronically-delivered tailored messaging intervention called Women's and Men's Hypertension Experiences and Emerging Lifestyle Intervention (WHEELS-I). Randomization will occur after phase 1 of the study which includes 2 weeks of an ad lib diet followed by 2 weeks of prepared pre-packaged DASH/SRD meals.
Behavioral: Performance of WHEELS-I in promoting DASH/SRD adoption
All participants will receive motivational interviewing (MI) based counseling. Participants in the MI + WHEELS-I arm will also receive the WHEELS-I electronically-delivered tailored messaging.
Other Names:
  • Phase 2
Active Comparator: Motivational Interviewing
Participants in this arm will receive motivational interviewing-based counseling with a registered dietitian to promote adoption of the sodium-restricted Dietary Approaches to Stop Hypertension (DASH/SRD) eating plan. Randomization will occur after phase 1 of the study which includes 2 weeks of an ad lib diet followed by 2 weeks of prepared pre-packaged DASH/SRD meals.
Behavioral: Performance of WHEELS-I in promoting DASH/SRD adoption
All participants will receive motivational interviewing (MI) based counseling. Participants in the MI + WHEELS-I arm will also receive the WHEELS-I electronically-delivered tailored messaging.
Other Names:
  • Phase 2

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Carotid-femoral Pulse Wave Velocity
Time Frame: Phase 1 of study, change between week 2 and week 4

Phase 1 primary hypothesis: greater reduction in carotid-femoral pulse wave velocity with DASH diet in individuals with salt-sensitive blood pressure

Change in velocity of pulse wave traveling between carotid and femoral artery; validated measure of arterial stiffness
Phase 1 of study, change between week 2 and week 4
Left Ventricular Mass Index
Time Frame: Phase 2 of study, change from baseline to 6 months

Left ventricular mass indexed to body surface area.

Larger/greater left ventricular mass index is associated with increased long-term risk of cardiovascular events, including the development of heart failure. Normal values for men are 49-115 g/m² and for women 43-95 g/m²
Phase 2 of study, change from baseline to 6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Global Longitudinal Left Ventricular Strain
Time Frame: Phase 1 of study, change between week 2 to week 4

Global longitudinal left ventricular strain (GLS), a sensitive measure of ventricular systolic function

GLS is calculated by dividing the reduction in length of a myocardial (heart) segment from the end of diastole (maximum relaxation) to the end of systole (maximum contraction) by the segment's original length at end-diastole (i.e. change in length/original length). GLS is averaged across six myocardial segments, is expressed in a percentage, and is negative by convention since cardiac segment length decreases during systole. The more negative/greater magnitude, the better the GLS.

Normal GLS is -18% to -22%. Low GLS is associated with long-term increased risk of cardiovascular events, including the development of heart failure.
Phase 1 of study, change between week 2 to week 4
Carotid-femoral Pulse Wave Velocity
Time Frame: Phase 2 of study, change from baseline to 6 months
Velocity of pulse wave traveling between carotid and femoral artery; validated measure of arterial stiffness
Phase 2 of study, change from baseline to 6 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Salt-sensitivity Phenotype
Time Frame: Phase 1 of study, change between week 2 and week 4

Salt-sensitive blood pressure means that blood pressure changes more than 'normal' when dietary sodium intake changes, i.e. increases or decreases in parallel with sodium intake. Having a salt-sensitive blood pressure pattern is an independent long-term risk factor for cardiovascular events. Variable testing approaches, blood pressure thresholds, and methods of blood pressure measurement have been proposed in the literature to define blood pressure salt-sensitivity.

In this study, we report "salt-sensitive" vs. "non salt-sensitive" as a binary variable. Change in 24-hour mean blood pressure of >= 4 mmHg between the ad-lib and home-delivered meal periods of Phase 1 defines the salt-sensitive blood pressure phenotype
Phase 1 of study, change between week 2 and week 4
24-hour Urinary Sodium Excretion
Time Frame: Phase 2 of study, change from baseline to 6 months
Measure of daily dietary sodium intake
Phase 2 of study, change from baseline to 6 months
Sodium-restricted DASH Diet Adherence by Food Frequency Questionnaire (FFQ)
Time Frame: Phase 2 of study, change from baseline to 6 months
Sodium-restricted DASH diet score on FFQ, measured by quintiles of intake in 8 dietary domains as compared with age- and sex-matched norms from NHANES national US survey data. Score ranges 8-40 points, with higher scores indicating greater adherence
Phase 2 of study, change from baseline to 6 months
Sodium-restricted DASH Diet Adherence
Time Frame: Phase 2 of study, change from baseline to 6 months
Analysis of 3-day food diaries by a Registered Dietitian, utilizing the Nutrition Data System for Research. DASH diet adherence score based on proportion of recommended daily intake in 9 domains, score ranges 0-9 points with higher scores indicating greater adherence
Phase 2 of study, change from baseline to 6 months
Clinic Systolic Blood Pressure
Time Frame: Phase 2 of study, change from baseline to 6 months
Change in systolic blood pressure obtained in clinic with automated brachial cuff
Phase 2 of study, change from baseline to 6 months
Clinic Diastolic Blood Pressure
Time Frame: Phase 2 of study, change from baseline to 6 months
Phase 2 of study, change from baseline to 6 months
Triglycerides
Time Frame: Phase 2 of study, change from baseline to 6 months
Serum triglyceride changes during dietary intervention
Phase 2 of study, change from baseline to 6 months
Urine Sodium and Potassium Ratios
Time Frame: Phase 2 of study, change from baseline to 6 months
Unitless ratio of urine sodium (in mmol) divided by urine potassium (in mmol), measured from spot samples taken from 24-hour urine samples.
Phase 2 of study, change from baseline to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
VA Office of Research and Development

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Scott L. Hummel, MD, VA Ann Arbor Healthcare System, Ann Arbor, MI

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 2, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 23, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 26, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 26, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 31, 2017

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 10, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 20, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CARA-009-16F
  • 9050 (Other Grant/Funding Number: VA CSR&D Merit)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

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