Clinical trial NCT02860156: Characterizing HIV-related Diastolic Dysfunction
Official title: Characterizing HIV-related Diastolic Dysfunction: A Cross Sectional Study Leveraging the NHLBI Heart Failure Clinical Research Network
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Failure
HIV
Diastolic Dysfunction
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2016-08-09
Enrollment: 195
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects who are receiving care at a site participating in the Heart Failure Clinical Research Network program, are HIV positive, have been on HAART for \>6 months and are virally suppressed will be screened for participation.

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.

Eligibility criteria: 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.)

Primary outcomes:
measure: persistent inflammation between HIV+/DD- and HIV+/DD+ subjects
timeFrame: baseline visit
measure: immune activation between HIV+/DD- and HIV+/DD+ subjects
timeFrame: baseline visit
measure: inflammation between HIV+/DD- and HIV+/DD+ subjects
timeFrame: baseline visit
measure: Perform phenomics of aggregate demographic data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects
timeFrame: baseline visit
measure: myocardial fibrosis by magnetic resonance imaging between HIV+/DD- and HIV+/DD+
timeFrame: baseline visit
measure: serum levels of biomarkers
timeFrame: baseline visit
measure: novel mechanisms underlying DD in HIV+ subjects as measured by proteomic and metabolomics panels
timeFrame: baseline visit
measure: the effect of DD on mechanics of the left atrium in HIV
timeFrame: baseline visit
measure: sub-clinical necrosis in HIV+/DD+ subjects
timeFrame: baseline visit
measure: myocardial stress in HIV+/DD+ subjects
timeFrame: baseline visit
measure: Perform phenomics of aggregate clinical data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects
timeFrame: baseline visit
measure: Perform phenomics of aggregate biomarker data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects
timeFrame: baseline visit
measure: Perform phenomics of aggregate electrocardiogram data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects
timeFrame: baseline visit
measure: Perform phenomics of aggregate imaging data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects
timeFrame: baseline visit
Secondary outcomes:
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: The Emory Clinic
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital-Washington University Hospital
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospital Cleveland Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Health System
state: Pennsylvania
city: Burlington
country: United States
facility: The University of Vermont
state: Vermont
Study officials:
affiliation: Duke University Health Services
name: Kevin Anstrom, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Harvard University
name: Eugene Braunwald, MD
role: STUDY_CHAIR
References:
citation: Colaco NA, Wang TS, Ma Y, Scherzer R, Ilkayeva OR, Desvigne-Nickens P, Braunwald E, Hernandez AF, Butler J, Shah SH, Shah SJ, Hsue PY. Transmethylamine-N-Oxide Is Associated With Diffuse Cardiac Fibrosis in People Living With HIV. J Am Heart Assoc. 2021 Aug 17;10(16):e020499. doi: 10.1161/JAHA.120.020499. Epub 2021 Aug 7.