Relationship Between Abnormal Myocardial Perfusion and Diastolic Dysfunction in Sickle Cell Disease Using PET

Sickle Cell Disease Clinical Trial

Official title:

An Evaluation of the Relationship Between Abnormal Myocardial Perfusion and Diastolic Dysfunction in Sickle Cell Disease Using PET (Stress-Rest) Myocardial Perfusion Imaging (MYPERS)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05583721
• Other study ID #: MYPERS
• Status: Recruiting
• Phase: Phase 2
• Start date: October 10, 2023
• Est. completion date: September 2026

Study information

• Verified date: February 2024
• Source: St. Jude Children's Research Hospital
• Contact: Parul Rai, MD
• Phone: 866-278-5833
• Email: referralinfo[@]stjude.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: September 2026
• Est. primary completion date: September 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 21 Years

Eligibility

Inclusion Criteria - Stratum A: Sickle cell patients with diastolic dysfunction

• 18 to 21 years of age

• Black

• Diagnosis of SCD of HbSS and HbSß0thalassemia 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 HbSß0thalassemia 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.

Exclusion Criteria - Stratum B:

• Diagnosed with three or more abnormal diastolic parameters (based on guidelines by American Society of echocardiography)

• 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.

Exclusion Criteria - Stratum C:

• All genotypes of SCD

• Diagnosed with three or more abnormal diastolic parameters (based on guidelines by American Society of echocardiography)

• Individual with hemoglobin level below the normal range for that age and sex

• 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/uncontro lled 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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

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.
• Lexiscan
Given IV prior to PET stress test

Diagnostic Test:
• Positron emission tomography
Participants will complete a onetime PET (stress-rest) myocardial perfusion scan.

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean and standard deviation of coronary flow reserve (CFR)	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.	Visit 2, approximately 4 weeks after study entry (procedure takes approximately one hour)
Primary	CFR difference among Stratum A, Stratum B, and Stratum C	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.	Visit 2, approximately 4 weeks after study entry (procedure takes approximately one hour)
Secondary	Relationship between decreased CFR (quantified with PET stress-rest myocardial perfusion imaging) and presence of abnormal diastolic parameters	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.	Visit 2, approximately 4 weeks after study entry (procedure takes approximately one hour)

External Links

•   ClinicalTrials Open at St. Jude
•   St. Jude Children's Research Hospital