Clinical trial NCT02874703: Mechanisms of Diastolic Dysfunction Among Persons With HIV Compared With Non-HIV Control Subjects
Official title: Mechanisms of Diastolic Dysfunction Among Persons With HIV Compared With Non-HIV Control Subjects
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV
Diastolic Dysfunction
Myocardial Fibrosis
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: President and Fellows of Harvard College
name: Nutrition Obesity Research Center at Harvard
First posted: 2016-08-22
Enrollment: 48
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: HIV positive and HIV negative participants

Brief summary: In this study, investigators plan to test two potential mechanisms contributing to diastolic dysfunction among asymptomatic persons with HIV who are on cART. The first proposed mechanism is that heightened systemic immune activation/inflammation in HIV contributes to myocardial inflammation, which in turn promotes myocardial fibrosis. The second mechanism is that ectopic fat deposition (increased visceral adiposity) in HIV relates to increased intramyocardial lipid content, which in turn contributes to diastolic dysfunction. Both HIV positive and HIV-negative participants will undergo cardiac MRI/ MRS imaging studies for evaluation of myocardial fibrosis, myocardial inflammation, and intramyocardial lipid content. Traditional markers of CVD risk, inflammatory markers/immune, hormonal markers, and markers of myocardial stretch/injury will be assessed in relation to cardiac MRI/MRS outcomes. Additionally, a small subset of participants with HIV will undergo longitudinal evaluations to assess effects of a clinically prescribed hormonal therapy on myocardial structure and function.


Eligibility criteria: HIV positive subjects

Inclusion Criteria:

* age ≥40 and ≤75 years
* documented HIV infection
* participant report that combination antiretroviral therapy (cART) (any regimen) has been taken stably without \> 4 week interruption for at least 180 days prior to study entry (report of switching regimens in that time frame is permissible)

Exclusion Criteria:

* CD4 \< 100 cell/mm3
* current active AIDS-defining illness
* current active or recent (not fully resolved within 30 days prior to study entry) systemic bacterial, fungal, parasitic, or viral infections (except HIV, HBV, human papillomavirus \[HPV\], or HCV)
* current active cancer
* clinical ASCVD, as defined by 2013 ACC/AHA guidelines (including previous diagnosis of AMI, ACS, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, PAD), by subject report
* clinical diagnosis of HFpEF or HFrEF, by subject report
* diagnosed DM on antihyperglycemic medication
* current, active use of immune suppressant medication including oral or intravenous corticosteroid or injectable biologic (oral ASA or NSAID use permitted)
* eGFR \<45 ml/min/1.73 m2 calculated by CDK-EPI
* standard contraindications to MRI procedure based on MGH MRI Patient Procedure Screening Form - including history of severe allergy to gadolinium
* use of lipid lowering agents including statin drugs, fibrates, ezetimibe, red yeast rice, niacin or omega-3 fatty acids (\>3 grams/day in standalone formulations) in the 90 days prior to study entry
* use of ACE inhibitor, ARB, or aldosterone receptor blocker in the 90 days prior to study entry
* pregnancy or breastfeeding (female subjects of reproductive potential)
* other medical, psychiatric, or psychological condition that, in the opinion of the study investigator, would interfere with completion of study procedures

HIV negative subjects:

Inclusion Criteria:

• age ≥40 and ≤75 years

Exclusion Criteria:

* HIV infection
* current active or recent (not fully resolved within 30 days prior to study entry) systemic bacterial, fungal, parasitic, or viral infections (except HIV, HBV, human papillomavirus \[HPV\], or HCV)
* current active cancer
* clinical ASCVD, as defined by 2013 ACC/AHA guidelines (including previous diagnosis of AMI, ACS, stable or unstable angina, coronary or other arterial revascularization, stroke, TIA, PAD), by subject report
* clinical diagnosis of HFpEF or HFrEF, by subject report
* diagnosed DM on antihyperglycemic medication
* current, active use of immune suppressant medication including oral or intravenous corticosteroid or injectable biologic (oral ASA or NSAID use permitted)
* eGFR \<45 ml/min/1.73 m2 calculated by CDK-EPI
* standard contraindications to MRI procedure based on MGH MRI Patient Procedure Screening Form - including history of severe allergy to gadolinium
* use of lipid lowering agents including statin drugs, fibrates, ezetimibe, red yeast rice, niacin or omega-3 fatty acids (\>3 grams/day in standalone formulations) in the 90 days prior to study entry
* use of ACE inhibitor, ARB, or aldosterone receptor blocker in the 90 days prior to study entry
* pregnancy or breastfeeding (female subjects of reproductive potential)
* other medical, psychiatric, or psychological condition that, in the opinion of the study investigator, would interfere with completion of study procedures

Primary outcomes:
measure: Extracellular Volume (ECV), a measure of myocardial fibrosis on Cardiac MRI
timeFrame: 3 weeks
Secondary outcomes:
measure: Myocardial Inflammation on Cardiac MRI
timeFrame: 3 weeks
measure: Intramyocardial fat on Cardiac MRI/MRS
timeFrame: 3 weeks
measure: Diastolic function on Cardiac MRI
timeFrame: 3 weeks
measure: Visceral Adiposity on MRI
timeFrame: 3 weeks
measure: Inflammation/ immune markers
timeFrame: 3 weeks
measure: Hormonal markers
timeFrame: 3 weeks
measure: Markers of myocardial stretch
timeFrame: 3 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
References:
citation: Toribio M, Fulda ES, Chu SM, Drobni ZD, Awadalla M, Cetlin M, Stanley TL, North CM, Nelson MD, Jerosch-Herold M, Szczepaniak LS, Burdo TH, Looby SE, Neilan TG, Zanni MV. Hot Flashes and Cardiovascular Disease Risk Indices Among Women With HIV. Open Forum Infect Dis. 2021 Jan 12;8(2):ofab011. doi: 10.1093/ofid/ofab011. eCollection 2021 Feb.
citation: Toribio M, Awadalla M, Cetlin M, Fulda ES, Stanley TL, Drobni ZD, Szczepaniak LS, Nelson MD, Jerosch-Herold M, Burdo TH, Neilan TG, Zanni MV. Brief Report: Vascular Dysfunction and Monocyte Activation Among Women With HIV. J Acquir Immune Defic Syndr. 2020 Oct 1;85(2):233-238. doi: 10.1097/QAI.0000000000002419.
citation: Zanni MV, Awadalla M, Toribio M, Robinson J, Stone LA, Cagliero D, Rokicki A, Mulligan CP, Ho JE, Neilan AM, Siedner MJ, Triant VA, Stanley TL, Szczepaniak LS, Jerosch-Herold M, Nelson MD, Burdo TH, Neilan TG. Immune Correlates of Diffuse Myocardial Fibrosis and Diastolic Dysfunction Among Aging Women With Human Immunodeficiency Virus. J Infect Dis. 2020 Mar 28;221(8):1315-1320. doi: 10.1093/infdis/jiz184.