Sickle Cell Disease
Conditions
Keywords
Sickle Cell Disease patients, Healthy controls, Abnormal diastolic heart function, Coronary Flow Reserve (CFR), Coronary microvasculature dysfunction, Myocardial perfusion reserve, Positron emission tomography (PET) imaging, PET (stress-rest) myocardial perfusion imaging
Brief summary
There is limited information on what causes injury to the heart in individuals with Sickle Cell Disease (SCD). Researchers in this study want to see if decreased blood flow to the heart during stress could be causing the heart damage seen in SCD patients. They also want to test people who don't have SCD to see if their hearts react the same way under stress. Primary Objective * To estimate the coronary flow reserve (CFR) (also referred to as myocardial perfusion reserve), as measured by PET stress-rest myocardial perfusion imaging, in SCD patients with and without diastolic dysfunction, and healthy controls. Secondary Objectives * To investigate the relationship between decreased CFR (quantified with PET stress- rest myocardial perfusion imaging) and presence of abnormal diastolic parameters
Detailed description
This study requires two visits. The first visit includes blood tests, an electrocardiogram (EKG), and an echocardiogram. The second visit includes a positron emission tomography (PET) stress test and a blood test. Subjects will be considered off-study one week after all post PET imaging study tests have been completed along with the next day and one-week follow-up phone calls are completed.
Interventions
DRUG[13N]NH3
Ammonia N 13 (a radioactive tracer) will be given per intravenous (IV) injection for diagnostic purposes in conjunction with positron emission tomography (PET) imaging.
DRUGLexiscan
Given IV prior to PET stress test
DIAGNOSTIC_TESTPositron emission tomography
Participants will complete a onetime PET (stress-rest) myocardial perfusion scan.
Sponsors
St. Jude Children's Research Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 21 Years
Healthy volunteers
Yes
Inclusion criteria
- Stratum A: Sickle cell patients with diastolic dysfunction * 18 to 21 years of age * Black * Diagnosis of SCD of HbSS and HbSβ0thalassemia genotypes * Three or more abnormal diastolic parameters (based on guidelines by American Society of echocardiography) Inclusion Criteria - Stratum B: Sickle cell patients without diastolic dysfunction * 18 to 21 years of age * Black * Diagnosis of SCD of HbSS and HbSβ0thalassemia genotypes * Two or less abnormal diastolic parameters Inclusion Criteria - Stratum C: Healthy controls * 18 to 21 years of age * Black * Two or less abnormal diastolic parameters
Exclusion criteria
- Stratum A: * Recent hospitalization for vaso-occlusive pain crisis or acute chest syndrome in last 4 weeks * Blood transfusion in the last 3 months * Individuals with signs, symptoms or EKG findings of acute myocardial ischemia, infarction or unstable angina * Individuals with history of VT/VF or SVT * Previous cardiac surgery * Known congenital heart disease (other than patent ductus arteriosus or Atrial septal defect) * Stenotic valvular disease or left main coronary artery stenosis * History of myo/pericarditis * Left ventricle systolic dysfunction * Cardiovascular instability/uncontrolled hypertension (h/o hypertensive urgency or emergency) * History of sinus node dysfunction or high grade AV nodal block * History of aborted sudden cardiac death or cardiac arrest * Current seizure disorder on AED * Pregnant/Breast-feeding * Any medical or social reason, which, in the opinion of the principal investigators would make the participation of the subject ill-advised.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean and standard deviation of coronary flow reserve (CFR) | Visit 2, approximately 4 weeks after study entry (procedure takes approximately one hour) | We will estimate the mean and standard deviation of CFR, as measured by PET myocardial blood flow reserve imaging, in young adult SCD patients with and without diastolic dysfunction and healthy controls. |
| CFR difference among Stratum A, Stratum B, and Stratum C | Visit 2, approximately 4 weeks after study entry (procedure takes approximately one hour) | We will compare whether the CFR is different among 3 predefined strata: Stratum A; SCD with diastolic dysfunction patients , Stratum B; SCD without dysfunction patient control, and Stratum C; normal healthy controls by one-way ANOVA or Kruskal-Wallis one-way analysis of variance, depending on the distribution of the data. If the difference exists, the pairwise comparison will be carried out by two sample t test or Wilcoxon rank sum test between two strata. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relationship between decreased CFR (quantified with PET stress-rest myocardial perfusion imaging) and presence of abnormal diastolic parameters | Visit 2, approximately 4 weeks after study entry (procedure takes approximately one hour) | The following is the grouping of diastolic parameters used in this study: Group 1: 0 or any 1 diastolic variable abnormal; Group 2: Any 2 variables abnormal; Group 3: Any 3 or more variables abnormal . We will first summarize the mean and standard deviation CFR values for each diastolic group. One-way ANOVA or Kruskal-Wallis one-way ANOVA will be used to explore whether there are any statistically significant differences between the means of these three groups. If a difference exists, the pairwise comparison will be carried out by two sample t test or Wilcoxon rank sum test between two groups. |
Countries
United States
Contacts
CONTACTParul Rai, MD
PRINCIPAL_INVESTIGATORParul Rai, MD
St. Jude Children's Research Hospital
Outcome results
None listed