Characterizing HIV-related Diastolic Dysfunction

Completed

• Conditions: HIV; Heart Failure; Diastolic Dysfunction

• Registration Number: NCT02860156
• Lead Sponsor: Duke University

Brief Summary

This is a multicenter clinical trial of a cross section of HIV+ patients with and without diastolic dysfunction. Approximately 200 HAART-treated virally suppressed HIV+ subjects (100 HIV+/DD+ \& 100 HIV+/DD-) will be enrolled. This study will evaluate biomarkers, phenomapping, metabolomics, cMRI, echocardiography to determine characteristics unique to this patient population.

Detailed Description

With the advent of highly active antiretroviral therapy (HAART), human immuno¬deficiency virus (HIV) type 1 infection has become a chronic disease. The proportion of patients expected to survive 5, 10, and 15 years after conversion in the HAART era are 99%, 93% and 89% respectively. With increased life expectancy and decreased morbidity from opportunistic infections, the importance of chronic complications associated with HIV-1 infection, including HF is becoming more evident. The advent of HAART has altered the epidemiology of HIV associated cardiomyopathy evolving from a primarily left ventricular systolic dysfunction to the growing recognition of left ventricular DD. DD is associated with the development of atrial fibrillation and heart failure (HF), and portends higher risk for all-cause mortality. Thus there is a widespread prevalence of cardiac abnormalities in HIV infected individuals that are associated with HF development and may represent a sub-clinical abnormality that may be potentially intervened upon to reduce the risk of subsequent HF. There are little data to understand the natural history and pathogenesis of cardiac abnormalities, specifically DD in HIV+ individuals, which may adversely affect the longevity and quality of life of these individuals.

Study Timeline

• Study First Submitted: 2016-07-28
• Study First Submitted QC: 2016-08-05
• Study First Posted: 2016-08-09
• Study Start: 2016-11-15
• Primary Completion: 2018-02-09
• Study Completion: 2018-02-09
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-28
• Last Update Posted: 2019-03-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 195

Inclusion Criteria

1. Age >40 years
2. Willingness and ability to provide informed consent
3. HIV antibody positive
4. On HAART for >6 months (HIV positive cohort only)
5. History of adequate viral suppression as defined by HIV RNA level <200 copies/mL in the past 6 months
6. LVEF >50% -

Exclusion Criteria

1. Past EF <50%
2. Moderate or severe valve stenosis or regurgitation, or past repair or replacement
3. Percutaneous or surgical revascularization or active angina
4. Persistent atrial fibrillation
5. BP>160mmHg SBP or >100mmHg DBP
6. Comorbid inflammatory disease (e.g. RA or SLE)
7. Active cancer or cancer chemotherapy treatment in the prior year (except skin cancer that did not require chemotherapy or radiation)
8. Chronic use of steroids or anti-inflammatory therapy
9. GFR <30 mL/min
10. Active in a clinical trial with investigational product
11. Pregnant or lactating females
12. Contraindication to cMR or gadolinium injection (such as severe claustrophobia, metal implants, etc.)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
immune activation between HIV+/DD- and HIV+/DD+ subjects	baseline visit	Compare immune activation between HIV+/DD- and HIV+/DD+ subjects.
the effect of DD on mechanics of the left atrium in HIV	baseline visit	To study the effect of DD on mechanics using left atrial strain during passive leg raise
Perform phenomics of aggregate demographic data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects	baseline visit
Perform phenomics of aggregate imaging data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects	baseline visit	imaging data
inflammation between HIV+/DD- and HIV+/DD+ subjects	baseline visit	To compare inflammation between HIV+/DD- and HIV+/DD+
novel mechanisms underlying DD in HIV+ subjects as measured by proteomic and metabolomics panels	baseline visit	To study the proteomic and metabolomics panels to enable identification of novel mechanisms underlying DD in HIV+ subjects
myocardial stress in HIV+/DD+ subjects	baseline visit	To study myocardial stress using NTProBNP levels in HIV+/DD+ subjects
persistent inflammation between HIV+/DD- and HIV+/DD+ subjects	baseline visit	Compare inflammation between HIV+/DD- and HIV+/DD+ subjects.
myocardial fibrosis by magnetic resonance imaging between HIV+/DD- and HIV+/DD+	baseline visit	To compare myocardial fibrosis by magnetic resonance imaging between HIV+/DD- and HIV+/DD+
serum levels of biomarkers	baseline visit	To identify systemic determinants (biomarkers) of DD in HIV+ persons
Perform phenomics of aggregate clinical data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects	baseline visit	Clinical data
Perform phenomics of aggregate biomarker data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects	baseline visit	Biomarker data
sub-clinical necrosis in HIV+/DD+ subjects	baseline visit	To study the sub-clinical necrosis using Troponin levels in HIV+/DD+ subjects
Perform phenomics of aggregate electrocardiogram data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects	baseline visit	electrocardiogram data

Trial Locations

Locations (12)

The Emory Clinic; 🇺🇸 Atlanta, Georgia, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Barnes-Jewish Hospital-Washington University Hospital; 🇺🇸 Saint Louis, Missouri, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

University Hospital Cleveland Medical Center; 🇺🇸 Cleveland, Ohio, United States

The University of Vermont; 🇺🇸 Burlington, Vermont, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

University of Pennsylvania Health System; 🇺🇸 Philadelphia, Pennsylvania, United States

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States