HFN_HIV: Characterizing HIV-related Diastolic Dysfunction

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02860156
• Collaborator: (none)
• Enrollment: 195
• Locations: 12
• Actual Duration (Months): 14.8
• Patients Per Site: 16.3
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure; HIV; Diastolic Dysfunction

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 Design

• Study Type: Observational
• Actual Enrollment: 195 participants
• Observational Model: Cohort
• Time Perspective: Cross-Sectional
• Official Title: Characterizing HIV-related Diastolic Dysfunction: A Cross Sectional Study Leveraging the NHLBI Heart Failure Clinical Research Network
• Actual Study Start Date: Nov 15, 2016
• Actual Primary Completion Date: Feb 9, 2018
• Actual Study Completion Date: Feb 9, 2018

Arms and Interventions

Arm	Intervention/Treatment
HIV+/DD+ Subjects are HIV positive and have diastolic dysfunction
HIV+/DD- Subjects are HIV positive and do not have diastolic dysfunction
HIV-/DD+ Subjects do not have HIV and have diastolic dysfunction

Outcome Measures

Primary Outcome Measures

1. persistent inflammation between HIV+/DD- and HIV+/DD+ subjects [baseline visit]

   Compare inflammation between HIV+/DD- and HIV+/DD+ subjects.

2. immune activation between HIV+/DD- and HIV+/DD+ subjects [baseline visit]

   Compare immune activation between HIV+/DD- and HIV+/DD+ subjects.

3. inflammation between HIV+/DD- and HIV+/DD+ subjects [baseline visit]

   To compare inflammation between HIV+/DD- and HIV+/DD+

4. Perform phenomics of aggregate demographic data to define risk factor phenotype signatures and relate these to HIV+/DD- and HIV+/DD+ subjects [baseline visit]

5. 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+

6. serum levels of biomarkers [baseline visit]

   To identify systemic determinants (biomarkers) of DD in HIV+ persons

7. 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

8. 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

9. sub-clinical necrosis in HIV+/DD+ subjects [baseline visit]

   To study the sub-clinical necrosis using Troponin levels in HIV+/DD+ subjects

10. myocardial stress in HIV+/DD+ subjects [baseline visit]

    To study myocardial stress using NTProBNP levels in HIV+/DD+ subjects

11. 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

12. 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

13. 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

14. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Emory Clinic	Atlanta	Georgia	United States	30322
2	Northwestern University	Chicago	Illinois	United States	60611
3	Tufts Medical Center	Boston	Massachusetts	United States	02111
4	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
5	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
6	Mayo Clinic	Rochester	Minnesota	United States	55905
7	Barnes-Jewish Hospital-Washington University Hospital	Saint Louis	Missouri	United States	63110
8	Duke University Medical Center	Durham	North Carolina	United States	27710
9	University Hospital Cleveland Medical Center	Cleveland	Ohio	United States	44106
10	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19104
11	University of Pennsylvania Health System	Philadelphia	Pennsylvania	United States	19104
12	The University of Vermont	Burlington	Vermont	United States	05401

Sponsors and Collaborators

• Duke University

Investigators

• Principal Investigator: Kevin Anstrom, PhD, Duke University Health Services
• Study Chair: Eugene Braunwald, MD, Harvard University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT02860156
• Other Study ID Numbers: Pro00074493
• First Posted: Aug 9, 2016
• Last Update Posted: Mar 4, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Heart Failure

Study Results

No Results Posted as of Mar 4, 2019