Clinical trial NCT01044901: Cardiovascular Complications of Sickle Cell Disease
Official title: Cardiovascular Complications of Sickle Cell Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sickle Cell Disease
Keywords: Sickle Cell Disease
Cardiac magnetic resonance imaging
Coronary Disease
Pulmonary Hypertension
Lead sponsor: University of Chicago
Sponsor class: OTHER
First posted: 2010-01-08
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects will be recruited from clinics at the University of Chicago as well as from the community via flyers posted at the University of Chicago and a web site posted on the University of Chicago Medical Center web site.

Brief summary: In this research study, we are using heart imaging exams and blood testing, in order to gain an improved understanding of the pulmonary (lung) hypertension and cardiovascular (heart) complications that often occur in sickle cell patients. Information gathered from the healthy volunteers that participate in this study will be compared to information from the sickle cell patients in this study in order to help further our understanding.

Detailed description: Cardiac magnetic resonance (CMR) has gained increasing clinical application in cardiopulmonary diseases. Due to its 3-dimensional nature, CMR is considered the gold-standard for quantifying left and right ventricular systolic function and size. Additionally, its high tissue contrast allows for a detailed characterization of myocardial tissue. Specifically, the use of techniques such as late gadolinium enhancement can be used to detect the presence of tiny amounts of myocardial scar. Other techniques have been shown to correlate strongly with myocardial iron content. Just as importantly, CMR perfusion imaging can accurately quantify myocardial blood flow and can provide tremendous insight into the function of the microcirculation. CMR's high spatial and temporal resolution, its 3-dimensional approach, its ability to characterize the tissue, and its ability to evaluate the micro- and macro-circulation make it a comprehensive technique for the evaluation of heart disease. Recently, one CMR study has already shown the presence of cardiac microvascular disease in a subset of adult sickle cell disease (SCD) patients in the absence of infarcted myocardium, myocardial iron overload, or coronary artery disease, increasing the evidence for the contribution of left heart disease to pulmonary hypertension (PH) development in these patients; unfortunately, strong conclusions could not be made because the study was underpowered. Thus, this proposal will leverage the advantages offered by CMR to better characterize and detect the PH and cardiopulmonary subphenotypes in the SCD patient population.

Eligibility criteria: Inclusion Criteria:

* Patients must be 18+
* Patients who were diagnosed with SCD confirmed by high-pressure liquid chromatography or hemoglobin electrophoresis will be eligible for the study
* Only patients in stable condition will be included
* Patients receiving transfusions will not be excluded

Exclusion Criteria:

* Patients with vaso-occlusive crises or an episode of acute chest syndrome within the previous four weeks (after 4 weeks have passed, the patients may be re-evaluated for eligibility)
* Patients with high degree heart block; active, hemodynamically significant, ventricular arrhythmias; unstable coronary syndromes; history of myocardial infarction within 1 month of the study.
* Contraindications to gadolinium-enhanced magnetic resonance examination such as severe claustrophobia, Pacemaker, defibrillators, cerebral aneurysm clips, or neurostimulator.
* Pregnancy
* Patients with sinus node dysfunction

Primary outcomes:
measure: MRI Parameter - LVEDVi, mL/cm2 (Measured Using Method of Disks, Controls Serve as Normal Ranges)
timeFrame: Parameter measured at baseline.
measure: MRI Parameter - LVESVi, mL/cm2 - (Measured Using Method of Disks, Controls Serve as Normal Ranges)
timeFrame: Parameter measured at baseline.
measure: MRI Parameter - LV Mass Index, g/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges)
timeFrame: Parameter measured at baseline.
measure: MRI Parameter - RVEDVi, mL/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges)
timeFrame: Parameter measured at baseline.
measure: MRI Parameter - RVESVi, mL/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges)
timeFrame: Parameter measured at baseline.
measure: MRI Parameter - LAi, mL/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges)
timeFrame: Parameter measured at baseline.
measure: MRI Parameter - RAi, mL/cm2, (Measured Using Method of Disks, Controls Serve as Normal Ranges)
timeFrame: Parameter measured at baseline.
measure: MRI Parameter - LVEF, %, (Measured Using Method of Disks, Controls Serve as Normal Ranges)
timeFrame: Parameter measured at baseline.
measure: MRI Parameter - RVEF, %, (Measured Using Method of Disks, Controls Serve as Normal Ranges)
timeFrame: Parameter at baseline.
measure: MRI Parameter - Late Gadolinium Enhancement, Performed Via Visual Inspection, Normally None Should be Present
timeFrame: Parameter measured at baseline.
measure: MRI Parameter - Myocardial T2-star, ms, Performed Using Decay Curves (Normal >20ms)
timeFrame: Parameter measured at baseline.
measure: MRI Parameter - Hepatic T2-star, ms, Performed Using Decay Curves, Normal >18ms
timeFrame: Parameter at baseline.
measure: MRI Parameter - Myocardial Perfusion Reserve Index, Measured Using Upslope Technique. Control Subjects Available for Normal Ranges
timeFrame: Parameter measured at baseline.
measure: MRI Parameter - Diastolic Dysfunction, Determined According to American Society of Echocardiography Guidelines
timeFrame: Parameter measured at baseline.
measure: MRI Parameter - Lateral E/e', Measured Using Doppler Echo. Controls Available as Normal Ranges
timeFrame: Parameter measured at baseline.
measure: MRI Parameter - Augmentation Pressure, See Controls for Normal Ranges
timeFrame: Parameter measured at baseline.
measure: MRI Parameter - Augmentation Index, See Control Subjects for Normal Ranges
timeFrame: Parameter measured at baseline.
measure: MRI Parameter - Systemic Systolic Blood Pressure
timeFrame: Parameter measured at baseline.
measure: MRI Parameter - Systemic Diastolic Blood Pressure, mm Hg
timeFrame: Parameter measured at baseline.
Secondary outcomes:
measure: Genome-Wide Gene Expression and Targeted Genetic Polymorphisms in SCD Patients Linked to a Quantitative Noninvasive-based PH Phenotype.
timeFrame: median follow up 3 years
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
Study officials:
affiliation: University of Chicago
name: Amit R Patel, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Desai AA, Patel AR, Ahmad H, Groth JV, Thiruvoipati T, Turner K, Yodwut C, Czobor P, Artz N, Machado RF, Garcia JGN, Lang RM. Mechanistic insights and characterization of sickle cell disease-associated cardiomyopathy. Circ Cardiovasc Imaging. 2014 May;7(3):430-437. doi: 10.1161/CIRCIMAGING.113.001420. Epub 2014 Mar 27.