- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03170375
Dietary Prevention of Heart Failure in Hypertensive Metabolic Syndrome
Study Overview
Status
Conditions
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 crossover-randomized 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
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Lauren E Herty, MPH RD
- Phone Number: (734) 222-7490
- Email: Lauren.Herty@va.gov
Study Contact Backup
- Name: Scott L Hummel, MD
- Email: Scott.Hummel@va.gov
Study Locations
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-
Michigan
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Ann Arbor, Michigan, United States, 48105-2303
- VA Ann Arbor Healthcare System, Ann Arbor, MI
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
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
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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).
|
Participants will receive the WHEELS-I electronically-delivered tailored messaging intervention in addition to motivational interviewing-based counseling.
Other Names:
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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.
|
Participants will receive the WHEELS-I electronically-delivered tailored messaging intervention in addition to motivational interviewing-based counseling.
Other Names:
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Experimental: DASH/SRD Diet
Participants in this arm will receive prepared, pre-packaged meals containing 1150mg of sodium.
|
Participants will be randomized to the sequence DASH/SRD-control diet or control diet-DASH/SRD, and consume the diets for 14 days each.
Other Names:
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Placebo Comparator: Control Diet
Participants in this arm will receive prepared, pre-packaged meals containing 5750mg of sodium.
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Participants will be randomized to the sequence DASH/SRD-control diet or control diet-DASH/SRD, and consume the diets for 14 days each.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Carotid-femoral pulse wave velocity
Time Frame: Phase 1 of study, change from baseline at the end of week 2 and week 4
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Velocity of pulse wave traveling between carotid and femoral artery; validated measure of arterial stiffness
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Phase 1 of study, change from baseline at the end of week 2 and week 4
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Left ventricular mass index
Time Frame: Phase 2 of study, change from baseline to 6 months
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Left ventricular mass indexed to height
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Phase 2 of study, change from baseline to 6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Ventricular stiffness
Time Frame: Phase 1 of study, change from baseline at the end of week 2 and week 4
|
Ventricular stiffness k, by Parametrized Diastolic Formalism analysis
|
Phase 1 of study, change from baseline at the end of week 2 and week 4
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Global longitudinal left ventricular strain
Time Frame: Phase 1 of study, change from baseline at the end of week 2 and week 4
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Global longitudinal left ventricular strain, a sensitive measure of ventricular systolic function
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Phase 1 of study, change from baseline at the end of week 2 and week 4
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Global left atrial strain
Time Frame: Phase 1 of study, change from baseline at the end of week 2 and week 4
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Global left atrial strain, a novel measure of atrial function
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Phase 1 of study, change from baseline at the end of week 2 and week 4
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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
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Phase 2 of study, change from baseline to 6 months
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Left atrial volume
Time Frame: Phase 2 of study, change from baseline to 6 months
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Left atrial volume by 3D echocardiography
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Phase 2 of study, change from baseline to 6 months
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Salt-sensitivity phenotype
Time Frame: Phase 1 of study, change from baseline at the end of week 2 and week 4
|
Change in 24-hour mean of >= 8 mmHg will define the salt-sensitive blood pressure phenotype
|
Phase 1 of study, change from baseline at the end of week 2 and week 4
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24-hour urinary sodium excretion
Time Frame: Phase 2 of study, change from baseline to 6 months
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Measure of dietary sodium intake
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Phase 2 of study, change from baseline to 6 months
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Sodium-restricted DASH diet adherence
Time Frame: Phase 2 of study, change from baseline to 6 months
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Sodium-restricted DASH diet score on Food Frequency Questionnaire, measured by complete or partial adherence to 9 dietary domains
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Phase 2 of study, change from baseline to 6 months
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Sodium-restricted DASH diet adherence
Time Frame: Phase 2 of study, months 1 and 6
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Analysis of 3-day food diaries by a Registered Dietitian, utilizing the Nutrition Data System for Research
|
Phase 2 of study, months 1 and 6
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Collaborators and Investigators
Investigators
- Principal Investigator: Scott L. Hummel, MD, VA Ann Arbor Healthcare System, Ann Arbor, MI
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID 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)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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