Myocardial Perfusion Imaging for Coronary Artery Disease

Recruiting at 1 trial location

Overseen By Kitty D Harrison, R.N

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Washington University School of Medicine

Must not be taking: Chemotherapy agents

Disqualifiers: Heart failure, Cardiomyopathy, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to image the heart using two substances: 13N-ammonia (a radioactive tracer used in PET scans) and Ga-68 Galmydar (a radiopharmaceutical). The aim is to better understand blood flow issues in individuals with coronary artery disease. Researchers seek to evaluate the effectiveness of these imaging methods in both individuals without heart problems and those with symptoms who have had normal or abnormal previous imaging tests. This trial may suit someone who has undergone heart imaging tests before, whether results showed no issues or indicated blood flow problems, and who has been referred for further heart examination. As an Early Phase 1 trial, this research focuses on understanding how these imaging methods work in people, offering participants a chance to contribute to groundbreaking advancements in heart imaging.

Do I need to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking chemotherapeutic agents, you must not have received them within 6 months of enrollment. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both 13N-ammonia and Ga-68 Galmydar are under study for heart imaging to assess blood flow. The FDA has approved 13N-ammonia for heart imaging, confirming its safety, though it involves some radiation, which might slightly increase cancer risk.

Ga-68 Galmydar is newer and remains under safety testing in humans. Animal studies have suggested it is safe enough to proceed with human testing. So far, researchers have found no major safety issues. However, as this is an early study, detailed safety information for humans is still being collected. Participants might experience some unknown side effects due to the research's early stage. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about 13N-ammonia and Ga-68 Galmydar in myocardial perfusion imaging because they offer potential improvements over traditional imaging agents like technetium-99m and thallium-201. Unlike standard agents, Ga-68 Galmydar provides high-resolution images that can better indicate blood flow in the heart, potentially leading to more accurate diagnoses of coronary artery disease. Additionally, the use of these radiotracers in PET imaging allows for more precise measurements of heart function and perfusion, which could improve patient outcomes by identifying issues earlier. This innovation in imaging might be able to detect coronary artery disease more accurately and quickly, helping doctors tailor treatments more effectively.

What evidence suggests that this trial's treatments could be effective for coronary artery disease?

Research has shown that Ga-68 Galmydar, an investigational imaging agent in this trial, shows promise for assessing blood flow in heart muscles. It helps identify early, potentially reversible changes in heart function. Meanwhile, 13N-ammonia PET imaging, another method under study, reliably predicts heart problems even when blood flow appears normal. This method commonly measures how well blood moves through the heart muscle. Both methods are under investigation in this trial to enhance heart disease detection. ^{6 7 8 9 10}

Who Is on the Research Team?

Pamela K Woodard, M.D

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-99 with a history of heart issues, specifically those who've had certain types of heart scans showing possible blockages and are referred for further testing. It's not suitable for pregnant or breastfeeding women, individuals over 500 lbs, those with severe claustrophobia, uncontrolled high blood pressure, recent major heart procedures, chemotherapy within the last six months, serious lung diseases with wheezing, severe heart failure or conditions that prevent stress testing.

Inclusion Criteria

I've had a heart scan showing reduced blood flow or a normal heart scan.

Exclusion Criteria

I have a type of heart disease not caused by blocked arteries.

Your blood pressure is too low at the start of the trial (systolic blood pressure less than 90 mmHg, diastolic blood pressure less than 50 mmHg).

I am unable to understand or sign the consent form.

What Are the Treatments Tested in This Trial?

Interventions

• 13N-ammonia
• Ga-68 Galmydar

Trial Overview

The study is evaluating [68Ga]Galmydar PET/CT imaging to see how well it can identify areas of the heart muscle that aren't getting enough blood flow in patients suspected to have coronary artery disease. This phase 0/1 trial will compare Galmydar images against traditional SPECT MPI results.

How Is the Trial Designed?

Group I: Symptomatic Patients with Normal Clinical SPECT or PET Experimental Treatment 1 Intervention

Patients in this group have had a clinical SPECT or PET MPI examination that is normal and do not have an invasive coronary angiography (ICA) referral. Participants will receive one \[68Ga\]Galmydar intravenous administration, 2 mCi during rest for the \[68Ga\]Galmydar PET MPI.

Group II: Symptomatic Patients with Abnormal Clinical SPECT or PET Experimental Treatment 1 Intervention

Patients in this group have had a clinical SPECT or PET MPI examination that is positive for ischemia in two myocardial segments and have been referred for invasive coronary angiography (ICA) as part of their routine standard-of-care. Subjects will undergo \[68Ga\]Galmydar PET/CT prior to any intervention. Participants will receive one \[68Ga\]Galmydar intravenous administration, 2 mCi during rest.

Group III: Asymptomatic Subjects (Normal Controls) Experimental Treatment 2 Interventions

Normal control subjects are asymptomatic, without history of cardiovascular disease or significant cardiovascular risk factors. These participants will receive two \[68Ga\]Galmydar intravenous administrations, 2 mCi during rest and 4 mCi during stress for the \[68Ga\]Galmydar PET MPI performed on Imaging Day-1. On Imaging Day-2, asymptomatic subjects will receive two single intravenous administrations each of 10 mCi of \[13N\]Ammonia during the rest and stress PET MPI. \[68Ga\]Galmydar and \[13N\]Ammonia imaging visits will be separated by a minimum of 3 days.

13N-ammonia is already approved in United States for the following indications:

Approved in United States as Ammonia N 13 for:

• Diagnostic PET imaging of the myocardium under rest or pharmacologic stress conditions to evaluate myocardial perfusion in patients with suspected or existing coronary artery disease

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

The use of 13N-labeled ammonia (13NH4+) for myocardial imaging has been shown to correlate well with actual blood flow in heart tissue, making it a reliable method for assessing heart health.

In a study involving 85 cardiac patients, 13NH4+ scintigraphy detected perfusion defects in 82% of patients with coronary artery disease, demonstrating its effectiveness in identifying heart issues, particularly in those with myocardial infarction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive evaluation of regional myocardial perfusion in 112 patients using a mobile scintillation camera and intravenous nitrogen-13 labeled ammonia. Walsh, WF., Harper, PV., Resnekov, L., et al.[2019]

In a study involving 14 healthy pigs, four gallium-68 (68Ga)-labeled tracers were evaluated for their effectiveness in PET imaging of myocardial perfusion, but all showed slow accumulation in the heart over time.

The best-performing tracer, [68Ga][Ga-(sal)2BAPDMEN]1+, had the highest myocardial uptake, yet there was no correlation between its uptake and actual myocardial perfusion measured with [15O]water, indicating these tracers are not suitable for clinical use in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of 68Ga-labeled tracers for PET imaging of myocardial perfusion in pigs. Tarkia, M., Saraste, A., Saanijoki, T., et al.[2015]

Cyclotron-produced nitrogen-13 labeled ammonia (13NH4+) is an effective and noninvasive agent for myocardial perfusion imaging, showing a strong correlation between regional uptake and tissue perfusion in patients with heart conditions.

This imaging technique allows for high-quality, reproducible myocardial images and is particularly useful for monitoring changes in regional perfusion in acute cardiac patients over short intervals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nitrogen-13-labeled ammonia for myocardial imaging. Walsh, WF., Fill, HR., Harper, PV.[2019]

N-13 ammonia positron computed tomography (PCT) provided high-resolution myocardial perfusion images that were clearer and of better quality than those obtained from single-photon emission computed tomography (SPECT), allowing for detailed assessment of heart structures and perfusion.

In patients with coronary artery disease (CAD), PCT effectively detected perfusion abnormalities during both rest and exercise, identifying issues in 74% of cases at rest and 95% during exercise, without any false positives, making it a reliable tool for evaluating heart function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Myocardial positron computed tomography using N-13 ammonia for evaluating coronary artery disease: comparison with thallium-201 emission computed tomography]. Tamaki, N., Yonekura, Y., Kodama, S., et al.[2016]

68Ga[Ga]-Galmydar shows potential as a PET imaging probe for myocardial perfusion, demonstrating stable retention in rat myocardium and quick excretion from the blood, indicating its efficacy for imaging applications.

Radiation dosimetry studies in mice suggest that 68Ga[Ga]-Galmydar has a low effective dose (0.021 mGy/MBq for males and 0.023 mGy/MBq for females), with the kidneys receiving the highest dose, making it a safe candidate for further human studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

68Ga[Ga]-Galmydar: Biodistribution and radiation dosimetry studies in rodents. Sivapackiam, J., Laforest, R., Sharma, V.[2021]

Myocardial-perfusion positron computed tomography (PCT) using 13N-ammonia is highly effective in detecting coronary artery disease (CAD), identifying 88% of stenosed vessels during exercise in a study of 25 subjects (6 normal and 19 with CAD).

The technique not only provides high-quality imaging but also allows for quantitative assessment of coronary reserve function, showing significant decreases in tracer concentration in CAD patients compared to normal segments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myocardial positron computed tomography with 13N-ammonia at rest and during exercise. Tamaki, N., Yonekura, Y., Senda, M., et al.[2019]

A novel method for producing [13N]ammonia from [13C]methanol using the 13C(p, n)13N reaction on a <10 MeV cyclotron was successfully developed, providing sufficient doses for preclinical PET imaging studies.

The produced [13N]ammonia showed no traces of methanol and effectively demonstrated cardiac perfusion imaging in mouse models, indicating its potential for diagnosing myocardial infarction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Production of [13N]ammonia from [13C]methanol on a 7.5&#8239;MeV cyclotron using 13C(p, n)13N reaction: Detection of myocardial infarction in a mouse model. Nkepang, GN., Gali, H., Houson, H., et al.[2020]

In a study involving 60 participants (20 normal subjects and 40 patients with coronary artery disease), 13N-ammonia myocardial PET scanning demonstrated high sensitivity (93%) for detecting coronary artery disease during exercise, especially in patients without prior myocardial infarction.

The technique effectively identified regional hypoperfusion in 96% of CAD patients with a history of myocardial infarction and successfully detected 89% of stenosed vessels, highlighting its efficacy in diagnosing coronary artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of coronary artery disease with 13N-ammonia and high-resolution positron-emission computed tomography. Yonekura, Y., Tamaki, N., Senda, M., et al.[2019]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40585149/

Multicenter Evaluation of Myocardial Flow Reserve as a ...

In this large multicenter cohort, MFR derived from 13 N-ammonia PET MPI is a strong, independent predictor of ACM, even in patients with normal perfusion.

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37748522/

13N-ammonia positron emission tomography for diagnosis ...

We aimed to investigate the differences in 13NH3 PET findings between INOCA and coronary artery disease (CAD). Methods: Overall, consecutive 433 ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT03170817

Quantitative 13N-Ammonia Cardiac Rest/Stress Digital ...

Patients with coronary artery disease undergo a N-13 ammonia rest/stress PET/CT scan. These patients are given: One 5-10 mCI N13-ammonia (13N-NH3) ...

4.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0167527323013852

13N-ammonia positron emission tomography for diagnosis ...

Using 13NH3 PET, Nakao et al. demonstrated that papillary muscle ischemia (PMI) was present in 11.8% of patients with coronary artery disease ( ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04343209

NCT04343209 | Ammonia N-13 Myocardial Blood Flow ...

This study is being conducted to provide access to and collect test data for an established nuclear medicine diagnostic imaging test called Positron ...

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siemens-healthineers.com

siemens-healthineers.com/en-us/molecular-imaging/petnet-solutions-mibr/ammonia-n13-injection

Ammonia N 13 Injection

IMPORTANT SAFETY INFORMATION · Radiation Risks Ammonia N 13 Injection may increase the risk of cancer. · Adverse Reactions

7.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2011/022119s001lbl.pdf

Ammonia N 13 Injection for intravenous use

Ammonia N 13 Injection is indicated for diagnostic Positron. Emission Tomography (PET) imaging of the myocardium under rest or pharmacologic stress conditions ...

8.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2007/22119s000_MedR.pdf

NDA #22-119, Ammonia N 13 Injection - accessdata.fda.gov

Furthermore, the recent scientific literature supports the safety and efficacy of ammonia N13 PET imaging of the myocardium to evaluate ...

9.

drugs.com

drugs.com/pro/ammonia-n-13.html

Ammonia N-13: Package Insert / Prescribing Information

Ammonia N 13 Injection is a radioactive diagnostic agent for Positron Emission Tomography (PET) indicated for diagnostic PET imaging of the myocardium.

10.

cms.gov

cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=N&NCAId=66&fromdb=true

NCA - Positron Emission Tomography (N-13 Ammonia) for ...

Use this page to view details for the decision Memo for Positron Emission Tomography (N-13 Ammonia) for Myocardial Perfusion (CAG-00165N).