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Dietary Prevention of Heart Failure in Hypertensive Metabolic Syndrome

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ClinicalTrials.gov Identifier: NCT03170375
Recruitment Status : Not yet recruiting
First Posted : May 31, 2017
Last Update Posted : July 24, 2018
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Heart Failure Behavioral: Performance of WHEELS-I in promoting DASH/SRD adoption Behavioral: Effects of a 2-week DASH/SRD intervention vs. control diet on HFpEF functional cardiovascular risk factors Not Applicable

Detailed Description:
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 : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Phase 1 of study: randomized crossover design, 14 days each of control vs. sodium-restricted DASH diet Phase 2 of study: randomized assignment, 6 months of motivational interviewing vs. motivational interviewing plus mobile application-based promotion of dietary adherence
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Dietary Prevention of Heart Failure in Hypertensive Metabolic Syndrome
Estimated Study Start Date : October 1, 2018
Estimated Primary Completion Date : December 30, 2022
Estimated Study Completion Date : December 30, 2022


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).
Behavioral: Performance of WHEELS-I in promoting DASH/SRD adoption
Participants will receive the WHEELS-I electronically-delivered tailored messaging intervention in addition to motivational interviewing-based counseling.
Other Name: 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.
Behavioral: Performance of WHEELS-I in promoting DASH/SRD adoption
Participants will receive the WHEELS-I electronically-delivered tailored messaging intervention in addition to motivational interviewing-based counseling.
Other Name: Phase 2

Experimental: DASH/SRD Diet
Participants in this arm will receive prepared, pre-packaged meals containing 1150mg of sodium.
Behavioral: Effects of a 2-week DASH/SRD intervention vs. control diet on HFpEF functional cardiovascular risk factors
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 Name: Phase 1

Placebo Comparator: Control Diet
Participants in this arm will receive prepared, pre-packaged meals containing 5750mg of sodium.
Behavioral: Effects of a 2-week DASH/SRD intervention vs. control diet on HFpEF functional cardiovascular risk factors
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 Name: Phase 1




Primary Outcome Measures :
  1. Carotid-femoral pulse wave velocity [ Time Frame: Phase 1 of study, change from baseline at the end of week 2 and week 4 ]
    Velocity of pulse wave traveling between carotid and femoral artery; validated measure of arterial stiffness

  2. Left ventricular mass index [ Time Frame: Phase 2 of study, change from baseline to 6 months ]
    Left ventricular mass indexed to height


Secondary Outcome Measures :
  1. 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

  2. Global longitudinal left ventricular strain [ Time Frame: Phase 1 of study, change from baseline at the end of week 2 and week 4 ]
    Global longitudinal left ventricular strain, a sensitive measure of ventricular systolic function

  3. Global left atrial strain [ Time Frame: Phase 1 of study, change from baseline at the end of week 2 and week 4 ]
    Global left atrial strain, a novel measure of atrial function

  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

  5. Left atrial volume [ Time Frame: Phase 2 of study, change from baseline to 6 months ]
    Left atrial volume by 3D echocardiography


Other Outcome Measures:
  1. 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

  2. 24-hour urinary sodium excretion [ Time Frame: Phase 2 of study, change from baseline to 6 months ]
    Measure of dietary sodium intake

  3. Sodium-restricted DASH diet adherence [ Time Frame: Phase 2 of study, change from baseline to 6 months ]
    Sodium-restricted DASH diet score on Food Frequency Questionnaire, measured by complete or partial adherence to 9 dietary domains

  4. Sodium-restricted DASH diet adherence [ Time Frame: Phase 2 of study, months 1 and 6 ]
    Analysis of 3-day food diaries by a Registered Dietitian, utilizing the Nutrition Data System for Research



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Ages Eligible for Study:   45 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

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): NCT03170375


Contacts
Contact: Alysia J Drummond, MPH RD CHES (734) 222-7563 Alysia.Drummond@va.gov
Contact: Scott L Hummel, MD Scott.Hummel@va.gov

Locations
United States, Michigan
VA Ann Arbor Healthcare System, Ann Arbor, MI Not yet recruiting
Ann Arbor, Michigan, United States, 48105
Contact: Alysia J Drummond, MPH RD CHES    734-222-7563    Alysia.Drummond@va.gov   
Contact: Scott L Hummel, MD       Scott.Hummel@va.gov   
Principal Investigator: Scott L. Hummel, MD         
Sponsors and Collaborators
VA Office of Research and Development
Investigators
Principal Investigator: Scott L. Hummel, MD VA Ann Arbor Healthcare System, Ann Arbor, MI

Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT03170375     History of Changes
Other Study ID Numbers: CARA-009-16F
9050 ( Other Grant/Funding Number: VA CSR&D Merit )
First Posted: May 31, 2017    Key Record Dates
Last Update Posted: July 24, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by VA Office of Research and Development:
obesity
sodium
DASH diet
hypertension
vascular stiffness
diastolic function

Additional relevant MeSH terms:
Heart Failure
Metabolic Syndrome X
Heart Diseases
Cardiovascular Diseases
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases