PET Imaging for Heart Function in Sickle Cell Disease

Overseen By Parul Rai, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores potential causes of heart damage in individuals with Sickle Cell Disease (SCD). Researchers use PET imaging, a scan that shows blood flow, to determine if the heart's blood flow during stress differs between SCD patients and healthy individuals. The goal is to understand whether reduced blood flow could lead to heart problems in SCD patients. Suitable participants include those diagnosed with SCD, regardless of heart function issues, and healthy individuals. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group.

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 prior data suggests that PET imaging is safe for assessing heart function in Sickle Cell Disease?

Research has shown that the treatments in this study are generally safe based on past data.

For [13N]NH3 (Ammonia N 13), studies have not reported specific side effects when used for imaging. However, a small risk of cancer exists, so researchers use the lowest possible doses to ensure safety.

The FDA has approved Lexiscan (regadenoson) for quick infusion. Previous studies, including those involving Sickle Cell Disease patients, have not identified major safety concerns.

Positron emission tomography (PET) scans, part of the imaging process, are considered safe and have been used in both animal and human studies without significant issues.

These treatments are generally well-tolerated, but researchers are studying them closely to ensure safety for everyone involved. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it uses PET imaging to explore heart function in individuals with sickle cell disease. Unlike traditional methods, which may rely on indirect markers or symptoms, PET imaging specifically uses [13N]NH3 and Lexiscan to directly visualize blood flow and heart performance. This approach offers a non-invasive and precise way to examine how sickle cell disease impacts the heart, potentially leading to earlier and more accurate interventions. By comparing sickle cell patients with and without diastolic dysfunction to healthy controls, researchers hope to uncover new insights into the cardiac effects of sickle cell disease.

What evidence suggests that PET imaging is effective for assessing heart function in Sickle Cell Disease?

Studies have shown that [13N]NH3 effectively detects heart problems, with a 98% success rate in identifying patients with coronary artery disease. This means it can reliably show how well blood flows to the heart. In this trial, [13N]NH3 will assess heart function in participants. Lexiscan, another tool in this trial, is under research for its potential to help with sickle cell disease by reducing inflammation. Although earlier studies did not show a significant reduction in certain immune cell activity, Lexiscan might still help reduce heart stress. Together, these tools aim to better understand heart function in people with sickle cell disease. ^{1 6 7 8 9}

Who Is on the Research Team?

Parul Rai, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• [13N]NH3
• Lexiscan
• Positron emission tomography

Trial Overview The 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.

How Is the Trial Designed?

Group I: Stratum C Experimental Treatment 3 Interventions

Healthy controls

Group II: Stratum B Experimental Treatment 3 Interventions

Sickle cell patients without diastolic dysfunction

Group III: Stratum A Experimental Treatment 3 Interventions

Sickle Cell patients with diastolic dysfunction

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Published Research Related to This Trial

The study demonstrated that myocardial blood flow (MBF) measurements at rest using 13N-ammonia PET are reproducible in healthy individuals, with no significant differences observed between baseline and follow-up measurements.

Pharmacologically induced hyperemia also showed consistent results, indicating that 13N-ammonia PET can reliably quantify changes in MBF and assess vasodilatory reserve over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reproducibility of measurements of regional resting and hyperemic myocardial blood flow assessed with PET. Nagamachi, S., Czernin, J., Kim, AS., et al.[2022]

Noninvasive PET imaging using [13N]ammonia is a promising diagnostic tool for accurately measuring myocardial blood flow in patients with coronary artery disease, which is crucial for assessing heart function and treatment responses.

The review details a tracer kinetic model that enhances the accuracy of blood flow estimates by addressing limitations in image resolution, demonstrating the quantitative capabilities of the [13N]ammonia technique through various studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative evaluation of myocardial blood flow with [13N]ammonia. Hutchins, GD.[2018]

N-13 ammonia PET imaging is highly effective for detecting coronary artery disease, outperforming traditional thallium-201 imaging methods, as shown in multiple studies.

This technique not only measures regional blood flow accurately but also assesses myocardial viability and differentiates between types of cardiomyopathy, although further research is needed to evaluate its cost-effectiveness in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrogen-13 ammonia perfusion imaging: relation to metabolic imaging. Niemeyer, MG., Kuijper, AF., Gerhards, LJ., et al.[2019]

In a study involving 12 children with sickle cell disease and 5 controls, arterial spin labeling (ASL) showed that cerebral blood flow (CBF) was higher in patients compared to controls, indicating potential alterations in blood flow due to the disease.

The study highlighted the importance of correcting CBF measurements for hematocrit and blood velocity, as these adjustments improved the accuracy of flow estimates and revealed clinically relevant asymmetries in some patients, although no direct link was found between CBF asymmetries and silent infarcts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Arterial spin labeling measurement of cerebral perfusion in children with sickle cell disease. Gevers, S., Nederveen, AJ., Fijnvandraat, K., et al.[2019]

Magnetic Resonance (MR) imaging is a promising tool for studying sickle cell disease, as it does not use ionizing radiation, making it safe for long-term monitoring of patients.

There is a need for more well-designed longitudinal studies using MR imaging to better understand the disease's pathophysiology and to objectively assess treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive diagnostic imaging in hemoglobinopathies. Rao, VM., Sebes, JI., Steiner, RM., et al.[2007]

The use of positron-emission tomography (PET) with 13NH3 allows for effective imaging of blood flow in the human brain, showing a strong correlation between 13NH3 uptake and normal blood perfusion in various brain structures.

This imaging technique also successfully identifies cerebral lesions and myocardial infarcts, demonstrating its safety and efficacy in quantitatively assessing hemodynamic and physiological functions in both the brain and heart.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tomographic images of blood pool and perfusion in brain and heart. Phelps, ME., Hoffman, EJ., Coleman, RE., et al.[2015]

In a study involving 14 children with sickle cell disease and 7 control subjects, cerebral blood flow (CBF) was found to be significantly higher in the sickle cell patients across all cerebral artery territories, indicating altered blood flow dynamics in these patients.

Despite higher overall CBF, some sickle cell patients exhibited decreased blood flow in specific areas of the brain, suggesting that conventional imaging may not fully capture the extent of cerebral blood flow abnormalities in this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sickle cell disease: continuous arterial spin-labeling perfusion MR imaging in children. Oguz, KK., Golay, X., Pizzini, FB., et al.[2016]

The newly developed whole-body multislice PET scanner allows for simultaneous imaging of the heart, providing valuable insights into regional blood flow and myocardial perfusion, particularly in coronary artery disease.

Using 13N labeled ammonia, PET scans can effectively identify perfusion defects in myocardial infarction and transient ischemia during exercise, making it a powerful diagnostic tool for heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive evaluation of regional myocardial perfusion with positron emission computed tomography. Torizuka, K., Yonekura, Y., Tamaki, N., et al.[2019]

Doppler tissue imaging (DTI) revealed that children with sickle cell anemia (SCA) have significantly higher right and left ventricular Tei indexes, indicating impaired myocardial function compared to healthy children, with 85 SCA patients studied.

There is a strong negative correlation between mean hemoglobin concentration and the Tei indexes, suggesting that lower hemoglobin levels are associated with worse cardiac function in SCA children, highlighting the importance of early screening for potential cardiac issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of cardiac functions in children with sickle cell anemia: doppler tissue imaging study. AboHadeed, HM., Zolaly, MA., Khoshhal, SQ., et al.[2018]

In a study of 6 patients with sickle cell disease (SCD) and a history of stroke, PET imaging was able to detect metabolic abnormalities in areas surrounding major vessel infarcts, which MRI alone did not fully capture.

However, PET was not effective in identifying issues related to small vessel disease, indicating that while it may enhance the evaluation of certain ischemic conditions in SCD, conventional imaging and neuropsychological testing remain the preferred methods for assessing most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of positron emission tomography in determining the extent of CNS ischemia in patients with sickle cell disease. Reed, W., Jagust, W., Al-Mateen, M., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5728341/

Randomized phase 2 trial of regadenoson for treatment of ... The primary outcome measure was a >30% reduction in the percentage of activated iNKT cells. Ninety-two patients with SCD were randomized to ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01788631

A Phase II Trial of Regadenoson in Sickle Cell Anemia This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug called Regadenoson (or Lexiscan) to ...

3. researchgate.net researchgate.net/publication/319344175_Randomized_phase_2_trial_of_regadenoson_for_treatment_of_acute_vaso-occlusive_crises_in_sickle_cell_disease

Randomized phase 2 trial of regadenoson for treatment ... PDF | Key Points Regadenoson did not reduce iNKT cell activation to a prespecified level when administered to patients with SCD.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3540605/

Sickle Cell Disease (SCD), iNKT Cells, and Regadenoson ... We have found two dose rates that are both safe and effective and now plan a controlled Phase 2B clinical trial to determine whether our highest dose, ...

5. digitalcommons.wustl.edu digitalcommons.wustl.edu/context/open_access_pubs/article/8240/viewcontent/Randomized_phase_2_trial_of_regadenoson_for_treatment_of_acute_vaso_occlusive_crises_in_sickle_cell_disease.pdf

Randomized phase 2 trial of regadenoson for treatment of ... Adenosine A2A receptor (A2AR) agonists have been shown to decrease tissue inflammation induced by hypoxia/reoxygenation in mice with sickle cell disease (SCD).

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01085201

Adenosine 2A Agonist Lexiscan in Children and Adults ... Lexiscan is drug that may prevent this inflammation and injury caused by the sickle shaped cells. This drug is approved by the FDA to be used as a fast infusion ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S000649711958781X

Regadenoson, An Adenosine 2A Receptor Agonist, Is Safe ... Regadenoson, An Adenosine 2A Receptor Agonist, Is Safe and Inhibits Invariant NKT Cells in Sickle Cell Disease. Author links open overlay panel

8. lexiscan.com lexiscan.com/ClinicalAttributes/ClinicalData

Clinical Data Overview | Lexiscan® (regadenoson) injection The efficacy and safety of Lexiscan were determined relative to Adenoscan® (adenosine) injection in two phase 3, randomized, double-blind, ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/21429807/

Targeting iNKT cells for the treatment of sickle cell disease An ongoing multi-center, dose-finding and safety trial of infused regadenoson, has been initiated and is providing preliminary data about its safety and ...