Overview

This trial is active, not recruiting.

Condition sickle cell disease
Treatment cardiac magnetic resonance imaging (cmr)
Sponsor Children's Hospital Medical Center, Cincinnati
Start date October 2013
End date September 2017
Trial size 26 participants
Trial identifier NCT02410811, 2012-4851

Summary

The purpose of this study is to use cardiac magnetic resonance imaging (CMR) and echocardiographic tissue Doppler imaging to demonstrate a unique restrictive cardiomyopathy of sickle cell disease. The investigators will characterize its frequency and how it might change (e.g., presence/absence and severity) over a 2-year period.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Observational model cohort
Time perspective prospective
Arm
Age 6 to 13.99 years Cardiac magnetic resonance imaging (CMR)
cardiac magnetic resonance imaging (cmr)
CMR is obtained on all participants in all arms/groups
Age 14 to 20.99 years Detectible and quantifiable TRJV with reported value Cardiac magnetic resonance imaging (CMR)
cardiac magnetic resonance imaging (cmr)
CMR is obtained on all participants in all arms/groups
Age ≥21 years Detectible and quantifiable TRJV with reported value Cardiac magnetic resonance imaging (CMR)
cardiac magnetic resonance imaging (cmr)
CMR is obtained on all participants in all arms/groups

Primary Outcomes

Measure
Frequency of RCM Phenotype
time frame: 3 years

Eligibility Criteria

Male or female participants from 6 years up to 65 years old.

Inclusion Criteria: - Sickle cell anemia (HbSS) or sickle-β°-thalassemia (HbSβ°) confirmed by hemoglobin separation and identification techniques - Ability to cooperate with and undergo CMR without sedation or anesthesia. - Ability to cooperate with and undergo echocardiogram - Written informed consent in accordance with the institutional policies and federal guidelines must be provided by the participant (if ≥18 years of age) or parent or legally authorized guardian (if the participant is <18 years of age) Minor participants ≥11 years of age will be requested to provide assent The following additional inclusion criterion applies to Age Stratum A: Age 6 to 13.99 years The following additional inclusion criteria apply to Age Stratum B: - Age 14 to 20.99 years - Detectible and quantifiable TRJV with reported value The following additional inclusion criteria apply to Age Stratum C: - Age ≥21 years - Detectible and quantifiable TRJV with reported value Exclusion Criteria: - Current chronic transfusion therapy (defined as regular, approximately monthly, transfusions of packed red blood cells given for at least 6 consecutive months for the treatment of prevention of SCD-related complications with the plan to continue this therapy at the time of potential enrollment) - Any contraindication to MRI or physical or behavioral factor that could degrade the quality of MRI data or interfere with a participant's tolerance of the MRI, such as permanent or semi-permanent metallic implants, including pacemakers and defibrillators, or severe claustrophobia - Known ventricular septal defect (VSD) documented in medical record - Estimated Glomerular Filtration Rate (eGFR) <60 mL/min/1.73 m2 (estimated by serum creatinine or cystatin-C) - Pregnancy (documented by serum or urine pregnancy test)

Additional Information

Official title Novel Cardiac Magnetic Resonance Imaging to Define a Unique Restrictive Cardiomyopathy in Sickle Cell Disease
Principal investigator Charles T Quinn, M.D.
Description Sickle cell disease (SCD) causes progressive cardiopulmonary morbidity, beginning in childhood, which can ultimately be fatal. As a group, cardiopulmonary complications, such as acute chest syndrome and sudden death, are now the most common causes of death in SCD, especially in adolescents and adults. Patients with SCD have features of both an anemia-related, high cardiac output state and a restrictive cardiomyopathy (RCM). The investigators propose that this unique RCM is an overlooked and understudied complication of SCD. RCM could explain the modest increases in pulmonary artery pressure in patients with SCD, as measured by cardiac catheterization or estimated by tricuspid regurgitant jet velocity (TRJV), which has often been attributed to a primary pulmonary arterial hypertension (PAH). RCM could also be the cause of unexplained sudden cardiac death in SCD, which is a feature of other forms of RCM. The investigators overarching hypothesis is that increased reactive oxygen species (ROS)-mediated angiotensin-1 receptor (AT1R)-TGFβ1 signaling is pro-fibrotic and, in combination with vaso-occlusive ischemia-reperfusion injury, results in an age-dependent, progressive RCM that can be detected by non-invasive cardiac imaging. This pilot, longitudinal, observational study uses a novel, comprehensive, multimodal cardiac imaging strategy, combining cutting-edge cardiac magnetic resonance imaging (CMR) and echocardiographic tissue Doppler imaging (TDI), to demonstrate the unique RCM of SCD, characterizing its frequency and the temporal evolution over a 2-year period. The investigators will also correlate the RCM phenotype with biomarkers of ROS and renin angiotensin system (RAS)-TGFβ1 signaling. This research could change the investigators understanding of how SCD affects the heart and lungs. The investigators propose studies that will change the current concept of primary pulmonary vasculopathy to a cardiomyopathy-centered model with secondary pulmonary vascular changes leading to sudden death. This translational pilot study will deliver a novel, clear, quantifiable CMR phenotype with established diagnostic performance that will be used in phase II/III clinical trials to test anti-fibrotic therapy to prevent or reverse SCD-related RCM.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Children's Hospital Medical Center, Cincinnati.