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

Primary Purpose

Sickle Cell Disease

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

[13N]NH3

Lexiscan

Positron emission tomography

About this trial

This is an interventional diagnostic trial for Sickle Cell Disease focused on measuring 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

Eligibility Criteria

18 Years - 21 Years (Adult)All SexesAccepts Healthy Volunteers

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.

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.

Sites / Locations

St. Jude Children's Research HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Stratum A

Stratum B

Stratum C

Arm Description

Sickle Cell patients with diastolic dysfunction

Sickle cell patients without diastolic dysfunction

Healthy controls

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT05583721

First Posted

October 13, 2022

Last Updated

September 14, 2023

Sponsor

St. Jude Children's Research Hospital

1. Study Identification

Unique Protocol Identification Number

NCT05583721

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 2023 (Anticipated)

Primary Completion Date

September 2025 (Anticipated)

Study Completion Date

September 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

St. Jude Children's Research Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sickle Cell Disease

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

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Stratum A

Arm Type

Experimental

Arm Description

Sickle Cell patients with diastolic dysfunction

Arm Title

Stratum B

Arm Type

Experimental

Arm Description

Sickle cell patients without diastolic dysfunction

Arm Title

Stratum C

Arm Type

Experimental

Arm Description

Healthy controls

Intervention Type

Drug

Intervention Name(s)

[13N]NH3

Other Intervention Name(s)

[N-13] Ammonia, azane, CAS# 34819-78-8

Intervention Description

Ammonia N 13 (a radioactive tracer) will be given per intravenous (IV) injection for diagnostic purposes in conjunction with positron emission tomography (PET) imaging.

Intervention Type

Drug

Intervention Name(s)

Lexiscan

Other Intervention Name(s)

Regadenoson

Intervention Description

Given IV prior to PET stress test

Intervention Type

Diagnostic Test

Intervention Name(s)

Positron emission tomography

Other Intervention Name(s)

PET

Intervention Description

Participants will complete a onetime PET (stress-rest) myocardial perfusion scan.

Primary Outcome Measure Information:

Title

Mean and standard deviation of coronary flow reserve (CFR)

Description

Time Frame

Visit 2, approximately 4 weeks after study entry (procedure takes approximately one hour)

Title

CFR difference among Stratum A, Stratum B, and Stratum C

Description

Time Frame

Visit 2, approximately 4 weeks after study entry (procedure takes approximately one hour)

Secondary Outcome Measure Information:

Title

Relationship between decreased CFR (quantified with PET stress-rest myocardial perfusion imaging) and presence of abnormal diastolic parameters

Description

Time Frame

Visit 2, approximately 4 weeks after study entry (procedure takes approximately one hour)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

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. 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Parul Rai, MD

Phone

866-278-5833

referralinfo@stjude.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Parul Rai, MD

Organizational Affiliation

St. Jude Children's Research Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

St. Jude Children's Research Hospital

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38105

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Parul Rai, MD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.

IPD Sharing Time Frame

Data will be made available at the time of article publication.

IPD Sharing Access Criteria

Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

Links:

URL

http://www.stjude.org

Description

St. Jude Children's Research Hospital

URL

http://www.stjude.org/protocols

Description

ClinicalTrials Open at St. Jude

Learn more about this trial

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

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