PET Imaging for Heart Function in Sickle Cell Disease
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: St. Jude Children's Research Hospital
Must not be taking: AEDs
Disqualifiers: Recent hospitalization, Blood transfusion, Myocardial ischemia, Congenital heart disease, Seizure disorder, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?
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
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. However, if you have a seizure disorder and are on anti-epileptic drugs (AED), you may be excluded from participating.
What data supports the effectiveness of the treatment involving PET Imaging for Heart Function in Sickle Cell Disease?
The research suggests that PET imaging can be useful in detecting impaired metabolism in areas around major vessel infarcts in sickle cell disease, which may help in understanding heart function. However, it is not generally effective for small vessel disease, and more studies are needed to confirm its usefulness.12345
How does PET imaging for heart function in sickle cell disease differ from other treatments?
PET imaging with 13N-ammonia is unique because it allows for noninvasive, detailed measurement of blood flow in the heart, which can help assess heart function in sickle cell disease. This approach is different from standard treatments as it provides a precise evaluation of myocardial perfusion (blood flow in the heart muscle) and can detect subtle changes in heart function that other methods might miss.678910
Research Team
PR
Parul Rai, MD
Principal Investigator
St. Jude Children's Research Hospital
Eligibility Criteria
This trial is for adults aged 18-21 with Sickle Cell Disease (SCD) and heart dysfunction, specifically those with abnormal diastolic parameters. It includes three groups: SCD patients with diastolic dysfunction, those without it, and healthy black individuals as controls.Inclusion Criteria
I am 18-21, Black, with SCD (HbSS or HbSβ0thalassemia), and have minimal heart issues.
I am a healthy Black individual aged 18-21 with two or fewer abnormal diastolic parameters.
I am 18-21, Black, with sickle cell disease and heart issues.
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/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
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
I have a complex heart condition or recent severe health issues.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Initial Assessment
First visit includes blood tests, an electrocardiogram (EKG), and an echocardiogram
1 day
1 visit (in-person)
PET Imaging and Stress Test
Second visit includes a positron emission tomography (PET) stress test and a blood test
1 day
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after PET imaging study tests with next day and one-week follow-up phone calls
1 week
Treatment Details
Interventions
- [13N]NH3 (Radiopharmaceutical)
- Lexiscan (Pharmacologic Stress Agent)
- Positron emission tomography (Imaging Agent)
Trial OverviewThe study aims to measure blood flow reserve in the heart using PET scans during rest and stress conditions. Researchers will compare results between SCD patients with varying levels of heart function and healthy people to understand the cause of heart damage in SCD.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: Stratum CExperimental Treatment3 Interventions
Healthy controls
Group II: Stratum BExperimental Treatment3 Interventions
Sickle cell patients without diastolic dysfunction
Group III: Stratum AExperimental Treatment3 Interventions
Sickle Cell patients with diastolic dysfunction
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
St. Jude Children's Research HospitalMemphis, TN
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Who Is Running the Clinical Trial?
St. Jude Children's Research Hospital
Lead Sponsor
Trials
451
Patients Recruited
5,326,000+
References
Arterial spin labeling measurement of cerebral perfusion in children with sickle cell disease. [2019]To evaluate the applicability of arterial spin labeling (ASL) cerebral blood flow (CBF) measurements in children with sickle cell disease (SCD).
Assessment of cardiac functions in children with sickle cell anemia: doppler tissue imaging study. [2018]The extent in which sickle cell anemia (SCA) impacts myocardial function in children is unclear. Doppler tissue imaging (DTI) was introduced as a new non-invasive echocardiographic method for assessment of ventricular systolic and diastolic functions. We undertook this study to assess subclinical impact of SCA on global myocardial performance in affected children using DTI and to correlate it with mean hemoglobin concentration.
Sickle cell disease: continuous arterial spin-labeling perfusion MR imaging in children. [2016]Cerebral blood flow (CBF) was measured with continuous arterial spin-labeling perfusion magnetic resonance (MR) imaging in 14 children with sickle cell disease and seven control subjects. Mean CBF values were higher in patients (P
Noninvasive diagnostic imaging in hemoglobinopathies. [2007]We have provided a global review of the current applications of newer modalities, particularly MR imaging, as applicable to the major manifestations of sickle cell disease, the most common hemoglobinopathy. There is a need for well-designed prospective longitudinal studies utilizing MR imaging to gain further insight into the pathophysiology of this intriguing disease. Additionally, MR imaging, because of lack of ionizing radiation, is ideally suited for long-term sequential studies and may thus provide an objective means for monitoring response to therapy.
Role of positron emission tomography in determining the extent of CNS ischemia in patients with sickle cell disease. [2019]Nearly 25% of patients with sickle cell disease (SCD) experience central nervous system morbidity involving both large and small vessel disease. Optimal imaging methods for determining the extent of ischemia are not known. Positron emission tomography (PET) has the unique ability to show tissue function as well as structure. Reports concerning patients with non-SCD neurodegenerative disorders suggest PET may be useful in determining prognosis. We compared magnetic resonance imaging, magnetic resonance angiography, and neuropsychological testing with PET prospectively. Six patients with SCD and a history of stroke, aged 10 to 28, were enrolled. PET studies were performed on an ECAT HR 47 scanner (Siemens/CTI, Knoxville, TN) using 18-F-fluorodeoxyglucose as a tracer. PET interpretations were conducted in blinded fashion. MRI studies found two patients with only small vessel disease and four with both large and small vessel disease. In two of four subjects with large vessel disease, PET showed a corresponding metabolic abnormality and also identified an area of hypometabolism extending beyond the anatomical lesion as shown by MRI. PET did not demonstrate an abnormality corresponding with small vessel disease. Detailed neuropsychological testing demonstrated cognitive dysfunction in all cases. For some patients, PET may add sensitivity in detecting impaired metabolism in the area surrounding a major vessel infarct. However, the technique does not appear to be generally useful in characterizing small watershed or deep white matter infarcts. Larger studies, to include control subjects and carefully selected untransfused SCD patients, are needed. A combination of conventional imaging and neuropsychological testing remains the preferred evaluation for most SCD patients with neurologic symptoms.
Noninvasive evaluation of regional myocardial perfusion with positron emission computed tomography. [2019]Positron emission computed tomography (PET) offers regional measurement of physiological and biochemical processes in vivo. We have constructed a whole-body multislice PET scanner, which provides 7 tomographic images at 16 mm intervals simultaneously. The high sensitivity with good spatial resolution of this system permits dynamic studies of the heart. PET scan of the heart was performed following intravenous bolus injection of 13N labeled ammonia. Serial dynamic images in normal cases showed early accumulation of tracer in the myocardium and rapid clearance from the cardiac blood pool. Delayed clearance from the blood and prolonged retention in the dorsal part of the lungs were observed in cases with myocardial infarction. A perfusion defect was clearly visualized in myocardial infarction except for infarction of the inferior wall. Transient ischemia was also visualized with exercise loading. Thus, PET with 13N ammonia is a valuable diagnostic tool for the evaluation of regional myocardial perfusion in coronary artery disease.
Tomographic images of blood pool and perfusion in brain and heart. [2015]A whole-body positron-emission transaxial tomograph (PETT III) was used to image the cross-sectional distribution of 13NH3 and 11CO-hemoglobin in the human brain and heart. Carotid and intravenous bolus injections of 13NH3 in the rhesus monkey had shown that 13NH3 is efficiently extracted by the brain and clears from it slowly (half-time, 40-50 min for carotid injections and 60-70 min for intravenous injections). The intravenous tomographic images in humans showed an excellent relationship between 13NH3 uptakes in the cortex, subcortical white matter, cerebellum, and brain stem and normal blood perfusion or flow in these structures. Cerebral lesions with high (metastasis) and low (stroke) blood flows showed correspondingly high and low uptakes of 13NH3. Large- and small-vascular structures of the brain were also clearly seen in 11CO-hemoglobin tomographic images. Normal myocardium and the ventricular chambers were well defined, and a transmural anterior myocardial infarct was clearly shown. The effective combination of positron transaxial tomography and compounds labeled with positron-emitters provides a safe new method for quantitatively imaging hemodynamic and physiologic functions of selected organs with good tomographic image quality.
Reproducibility of measurements of regional resting and hyperemic myocardial blood flow assessed with PET. [2022]PET with 13N-ammonia permits the noninvasive quantification of myocardial blood flow (MBF) in humans. The present study was done to assess the reproducibility of quantitative blood flow measurements at rest and during pharmacologically induced hyperemia in healthy individuals.
Quantitative evaluation of myocardial blood flow with [13N]ammonia. [2018]The clinical need for diagnostic tools that accurately assess the functional status of the heart in patients with coronary artery disease and their response to therapeutic interventions has driven the development of noninvasive PET imaging techniques for measuring myocardial blood flow. A method for the estimation of myocardial blood flow based upon the pharmacokinetic properties of [13N]ammonia measured with a PET imaging system is described in this review. The formation of the [13N]ammonia tracer kinetic model for quantitative estimates of myocardial blood flow is presented. In addition, methods for coupling the tracer kinetic model with a simple geometric model representing the heart and bloodpool are described to minimize the bias introduced by the limited image resolution achieved in PET studies of the heart. Studies that have been performed to demonstrate the quantitative capabilities of the [13N]ammonia technique are also presented.
Nitrogen-13 ammonia perfusion imaging: relation to metabolic imaging. [2019]PET provides an advanced imaging technology that permits the accurate definition of regional tracer distribution. In combination with N-13 ammonia, PET allows for the sensitive and specific detection of coronary artery disease. Results of several studies indicate the superiority of this approach compared with standard thallium-201 tomographic imaging. In addition, regional blood flow can be accurately measured with N-13 ammonia PET, and this approach can be used in conjunction with pharmacologic stress imaging to quantify regional flow reserve. In combination with metabolic markers, N-13 ammonia is capable of assessing myocardial viability. Furthermore, the N-13 ammonia PET approach may differentiate among various forms of cardiomyopathy. More studies are needed to define the cost-benefit ratio of the N-13 ammonia PET technique for the management of patients with coronary artery disease or cardiomyopathy.