Clinical trial NCT02399384: Pericardial Fat and Inflammation in HIV Patients and Controls
Official title: Myocardial Adipose Inflammation and Pericardial Adipose Volume as Markers for Coronary Artery Disease In HIV Positive Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Coronary Artery Disease
Human Immunodeficiency Virus (HIV)
Keywords: Cardiac Magnetic Resonance (CMR)
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
First posted: 2015-03-26
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV infected persons with a history of a positive or negative coronary angiography or cardiac computed tomography angiography (CTA) will be invited to participate in this study from the Infectious Diseases Center practice where there are 1800 persons receiving care. Additionally 4 subjects will be recruited from the cardiology practice at UCMC who have coronary artery disease but do not have HIV.

Brief summary: The investigators propose to correlate 1) cardiac MRI pericardial adipose volume, 2) the presence of pericardial monocytes and 3) circulating immune biomarkers in persons with and without CHD and HIV infection compared to seronegative controls with known CHD. The investigators aim to test the hypothesis that higher amounts of pericardial fat deposition and increased presence of monocytes within this adipose tissue are associated with underlying coronary artery disease in persons with HIV infection as measured by cardiac MRI.

Detailed description: Methods and Procedures:

Screening Assessments Patients who potentially meet inclusion criteria will be identified through the Infectious Disease Center and/or the cardiac catheterization laboratory who have had a coronary angiogram or cardiac CT angiogram, with or without evidence of CAD. Their records will be reviewed for inclusion and exclusion criteria and informed consent will be obtained prior to any research related procedures by a member of the research team for this project.

A screening visit will be done to obtain informed consent. BUN and Creatinine will be done at screening to ensure the safety of the MRIprocedure.

In HIV-infected subjects who have not had HIV-1 RNA or CD4+ lymphocyte tests obtained in the last 60 days, these will be done at screening.

Screening visits will last approximately 30-60 minutes.

Entry Visit - MRI The entry visits will occur within 14 days of the screening assessment. All female patients of child bearing potential will have a negative pregnancy test.

If BUN/Creatinine results are greater than 14 days old, they will be repeated STAT prior to beginning MRI procedure.

Whole blood will be drawn for biobanking (PBMCs, Plasma and Serum) as well as fasting lipids will be obtained.

An IV will be started in the MRI laboratory. All participants will undergo an initial cardiac MRI with contrast for the evaluation of cardiac function, chamber size, resting perfusion, pericardial adipose volume/mass, myocardial edema and determination of infarction.

The GE Signa Horizon 1.5T Magnet will be used to obtain all images. Sequences obtained will include Double IR, Triple IR, T2 Stars, SSFP and delayed gadolinium enhancement imaging.

After the initial CMR on day 1, Feraheme 5 mg/kg IV will be administered. Feraheme (30 mg/mL) is available for intravenous injection in single use vials. Each vial contains 510 mg of elemental iron in 17 mL.

Feraheme will be administered as an undiluted intravenous injection delivered at a rate of up to 1 mL/sec (30 mg/sec) through a filtered needle.

Patients will be monitored for 1 hour after administration for signs of allergic reaction.

The total amount of time for the Entry visit will be about 4 hours. Day 2 or 3 - repeat MRI A second, limited cardiac MRI will be obtained 48-72 hours after injection of Feraheme to determine the presence of monocyte/macrophages in adipose tissue.

The GE Signa Horizon 1.5T Magnet will be used to obtain all images. Imaging with T2 Stars and Triple IR sequences.

Data To be Collected:

MRI data to be collected will include:

Left ventricular and right ventricular ejection fractions Left ventricular wall motion Edema Resting myocardial perfusion Pericardial adipose tissue volume T2 star values of pericardial fat pre-Feraheme and post-Feraheme Late gadolinium enhancement (scar assessment and distribution) Valvular assessment Extracardiac assessment - pericardial effusion, pleural effusion, ascites Vital signs (height, weight, blood pressure, heart rate, BSA) Additional Data to be collected if available from the clinical record. Left Heart catheterization Presence or absence of coronary artery disease. The general anatomy, lesion location and severity, presence, location and type of stents, left ventricular end diastolic pressure, systemic blood pressure, aortic valve gradient Echocardiogram Ejection fraction Regional wall motion abnormalities Inducible ischemia if a stress echo was performed Nuclear Stress study Presence or absence of ischemia or infarction Distribution of perfusion abnormalities. Ejection fraction TID (transient ischemic dilatation) End Diastolic Volume End Systolic Volume Medical History (Presence or Absence of ) Sociodemographic information (age, race/ethnicity, etc) HIV related medical information Myocardial Infarction Hypercholesterolemia Hypertension Ventricular Tachycardia Stent Placement Bypass Surgery Diabetes Peripheral Vascular Disease Stroke Smoking (Lifetime Pack-year history and Current status) Family History of Heart Disease Medications Current use in the last 30 days of Anti-hypertensive (Beta Blockers, Calcium Channel Blockers, Ace Inhibitors, Angiotensin Receptor Blockers, Alpha Antagonists) Current use in the last 30 days of Diuretics Lifetime use of Statins Current use in the last 30 days of Insulin or other anti-diabetic medications Lifetime use of Antiretroviral Therapy Laboratory Results HIV-1 Viral Load in the last year Nadir CD4 Count and CD4 count in the last year (include percentages) CD8/CD8 percent in the last year Troponins ( around time of MI if applicable) Most recent Creatinine within 90 days of study entry Most recent BUN within 90 days of study entry If subject has diabetes, hemoglobin A1C or Fructosamine levels in the last year.

Primary endpoints Pericardial adipose tissue volume Change in T2 star value (assessment for iron deposition as a marker for inflammation) Secondary endpoints Correlation of inflammatory biomarkers with Pericardial adipose tissue volume and change in T2 star value Correlation of prior HIV related and Coronary Heart Disease risk factors and events with inflammatory biomarkers, pericardial adipose tissue volume and change in T2 star value.

Data Analysis Data will be stored in a RedCap data base. Statistical analysis will be performed using MedCalc. Continuous variables will be analyzed using analysis of Variance (ANOVA). Non-continuous variables will be analyzed using chi square tests.

Data Monitoring This study will be monitored by a trained coordinator not involved in the research project after enrollment of the first subject, fifth subject and last subject. The monitoring plan will include 100% verification of consent process and inclusion and exclusion criteria. Monitoring for appropriate documentation and collection of study data will be done on the first three subjects and after completion of the last subjects on all study participants. Additional monitoring will be conducted based on risk based assessment of the monitor.

Data Safety Monitoring Board (DSMB) No DSMB will be established for this study. The risks of MRI and phlebotomy are low and there are no test agents being used that are not Food and Drug Administration (FDA) approved. The investigators will monitor closely for adverse events and if an unanticipated number or severity of events occur, the Institutional Review Board (IRB) will be notified and a DSMB will be convened.

Data Storage and Confidentiality:

Participant medical information will be stored electronically in a Redcap database. Each subject will have a unique study ID assigned to their data.

The names and medical record numbers of the research participants will be kept under lock and key and separate from the actual research data in recap. No identifying information will be present in the research database.

Access to participant medical information contained within this research project will be restricted to involved investigators and study personnel.

Password protection of data files will be used. Any paper based data pertaining to individuals will be stored in a locked secure location.

De-identified participant medical record information will be stored for an indefinite period of time per institutional policies at the University of Cincinnati (UC).

Setting: University of Cincinnati Medical Center, and affiliated MRI facilities

Laboratory Methods and Facilities:

Peripheral blood mononuclear cells, plasma and serum will be obtained and stored for subsequent measurement of; hsCRP, IL-6, D-dimer, sCD163, CXCL10, flow cytometry for measures of monocyte activation and additional studies.

DNA will be isolated and may be sent for genetic testing related to inflammation, lipid disorders and atherosclerosis.

Fasting lipids will be obtained on the day of the cardiac MRI CD4 counts and HIV RNA quantitation obtained within 60 days of the cardiac MRI will be recorded.

Estimated Period of Time to Complete the Study: 12 months, ending June 30, 2015.

Eligibility criteria: Inclusion Criteria:

* \> 18 years of age
* History of HIV disease or no history of HIV
* Prior history of left heart catheterization or CTA indicating the presence or absence of CAD.

Exclusion Criteria:

* Unable to have a contrast enhanced cardiac MRI, (i.e. ferromagnetic foreign body, inability to follow verbal instructions, prior history of allergic reactions to gadolinium, history of nephrogenic systemic fibrosis, severe renal dysfunction GFR\<30 ml/min/1.73 m2, or severe claustrophobia/anxiety);
* Chronic kidney disease patient undergoing hemodialysis or peritoneal dialysis
* Allergy to Iron Compounds;
* Pregnant females.

Primary outcomes:
measure: Pericardial adipose tissue volume
timeFrame: On baseline imaging
Secondary outcomes:
measure: Adipose spin spin relaxivity as measured by T2 star time
timeFrame: At baseline and 48-72 hours later
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: David M Harris, MD
role: PRINCIPAL_INVESTIGATOR
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