Nuclear Imaging for Cardiomyopathy

(DISSOLvE Trial)

Overseen By Ahmad Masri, MD MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Oregon Health and Science University

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 62

Duration: 120-140 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a special imaging technique can aid in understanding transthyretin amyloid cardiomyopathy, a condition characterized by abnormal protein buildup in the heart. The technique uses a tracer called 99m-technetium pyrophosphate (Tc-99m PYP) to produce detailed heart images. The goal is to observe heart changes over time in individuals already enrolled in the CARDIO-TTRansform study. Participants with transthyretin amyloid cardiomyopathy who are part of the CARDIO-TTRansform trial may be suitable for this trial. As a Phase 2 trial, this research measures the effectiveness of the imaging technique in an initial, smaller group, allowing participants to contribute to significant advancements in understanding heart disease.

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

The protocol does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

What prior data suggests that 99m-technetium pyrophosphate scintigraphy is safe for nuclear imaging in cardiomyopathy?

Research has shown that a special imaging test called 99m-technetium pyrophosphate scintigraphy is generally safe and well-tolerated by patients. In a study with 171 participants, this test effectively identified 91% of those with transthyretin amyloid cardiomyopathy (ATTR-CM) and 92% of those without it. The studies reported no major safety issues or side effects from using this test. This suggests that the procedure is safe and reliably detects heart conditions without causing harm. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about 99m-technetium pyrophosphate scintigraphy for cardiomyopathy because it offers a novel approach to diagnosing transthyretin amyloid cardiomyopathy. Unlike standard treatments that manage symptoms or slow disease progression, this technique uses a radioactive tracer to provide detailed imaging of the heart. It helps identify amyloid deposits more accurately and earlier than traditional methods. This precise imaging can lead to better-targeted treatments and improved patient outcomes, sparking interest in its potential to transform care for this condition.

What evidence suggests that 99m-technetium pyrophosphate scintigraphy is effective for cardiomyopathy?

Research has shown that a special imaging test called 99m-technetium pyrophosphate scintigraphy effectively diagnoses transthyretin amyloid cardiomyopathy (ATTR-CM). This test uses a tracer to highlight affected areas in the heart. Studies have demonstrated its usefulness in early detection, which is crucial for prompt treatment. In this trial, patients with transthyretin amyloid cardiomyopathy will undergo serial Tc-99m PYP imaging at baseline, week 61, and the trial's end. Additionally, evidence indicates that patients with hereditary ATTR-CM show changes in heart images when treated, suggesting that this test can also monitor treatment effectiveness. Overall, this imaging method excels in detecting and tracking the progression of ATTR-CM. ^{1 2 3 4 6}

Who Is on the Research Team?

Ahmad Masri, MD MS

Principal Investigator

Oregon Health and Science University

Are You a Good Fit for This Trial?

This trial is for patients with Transthyretin Amyloid Cardiomyopathy or related heart conditions who are already part of the CARDIO-TTRansform study. They must be willing to consent and undergo additional imaging tests, and have had a specific heart scan within the last year.

Inclusion Criteria

Patients have to meet the inclusion and exclusion criteria of CARDIO-TTRansform trial to be enrolled.

Patient willing to consent for the study and undergo the study procedures.

I was eligible for or enrolled in the CARDIO-TTRansform study and had specific heart scans within the last year.

Exclusion Criteria

N/A

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Participants undergo baseline Tc-99m PYP imaging to assess myocardial uptake

1 week

1 visit (in-person)

Treatment

Participants receive treatment as part of the CARDIO-TTRansform trial and undergo serial imaging

120-140 weeks

Multiple visits (in-person) for imaging at baseline, week 61, and end of trial

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 99m-technetium pyrophosphate scintigraphy

Trial Overview The study is testing how well a tracer called 99m-technetium pyrophosphate shows up in heart scans over time. This will help understand changes in patients' hearts during the CARDIO-TTRansform clinical trial.

How Is the Trial Designed?

Group I: Patients with transthyretin amyloid cardiomyopathy enrolled in CARDIO-TTRansform Experimental Treatment 1 Intervention

Patients will undergo serial Tc-99m PYP imaging at baseline, week 61 and end of trial

99m-technetium pyrophosphate scintigraphy is already approved in United States, European Union for the following indications:

Approved in United States as Technetium Tc-99m pyrophosphate for:

• Diagnostic imaging scans for the bones, heart, and gastrointestinal tract
• Detection of transthyretin cardiac amyloidosis

Approved in European Union as Technetium Tc-99m pyrophosphate for:

• Diagnostic imaging scans for the bones, heart, and gastrointestinal tract

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

Ionis Pharmaceuticals, Inc.

Industry Sponsor

Trials

151

Recruited

27,800+

Dr. Brett P. Monia

Ionis Pharmaceuticals, Inc.

Chief Executive Officer since 2020

PhD in Pharmacology from the University of Pennsylvania, BSc in Molecular Biology and Analytical Chemistry from Stockton State College

Dr. Eric Bastings

Ionis Pharmaceuticals, Inc.

Chief Medical Officer

MD

Published Research Related to This Trial

In a study involving 15 patients undergoing adriamycin treatment for cancer, technetium-99m pyrophosphate imaging revealed abnormal heart accumulation in several patients.

The abnormal accumulation was particularly noted in patients with poor-risk factors, such as prior radiation therapy, cyclophosphamide treatment, and existing ischemic heart disease, suggesting a potential link between these factors and heart health during cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myocardial imaging with Cc-99m pyrophosphate in patients on adriamycin treatment for neoplasia. Chacko, AK., Gordon, DH., Bennett, JM., et al.[2015]

Technetium 99m labeled pyrophosphate is a safe and noninvasive imaging technique that effectively identifies areas of reduced blood flow in the heart for patients with coronary artery disease.

This imaging method has shown to be useful in assessing improvements in blood supply to the heart after coronary artery bypass surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of myocardial revascularization utilizing Tc-99m pyrophosphate. Liddicoat, JE., Bekassy, SM., Johnson, PC., et al.[2015]

In a case study of a 78-year-old man with an acute myocardial infarction, technetium-99m-pyrophosphate (99mTc-PYP) imaging revealed extensive distribution in the heart, indicating significant myocardial damage.

Despite severe coronary artery disease and a total occlusion in two major arteries, the patient was treated conservatively and discharged in stable condition after 20 days, suggesting that conservative management can be effective in certain high-risk cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myocardial damage of the entire ventricular region in a patient with acute myocardial infarction. Kawamata, H., Kawasaki, T., Sugihara, H., et al.[2020]

In a study of 15 patients, technetium Tc-99m pyrophosphate (PYP) provided high-quality images for cerebrospinal fluid (CSF) leak imaging, confirming its effectiveness as a diagnostic tool.

No adverse reactions were reported during the imaging procedures, indicating that Tc-99m PYP is a safe alternative for CSF leak imaging following the discontinuation of previous radiopharmaceuticals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technetium Tc-99m pyrophosphate for cerebrospinal fluid leaks: radiopharmaceutical considerations. Ponto, JA., Graham, MM.[2016]

A 99mTc-Pyrophosphate (99mTc-PYP) myocardial scan showed positive results in a child with congenital cyanotic heart disease, indicating its potential utility in diagnosing complications like bacterial endocarditis.

This case highlights the effectiveness of 99mTc-PYP scans in identifying myocardial involvement in pediatric patients with complex heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

99mTc-pyrophosphate imaging: bacterial endocarditis. Sty, JR., Chusid, MJ.[2019]

Cardiac patients can safely undergo 99mTc-pertechnetate (99mTc04) imaging 24 hours after receiving 99mTc-stannous pyrophosphate (99mTc-PYP), allowing for effective assessment of left ventricular function.

The method utilizes residual tin from the initial injection to label red blood cells with 99mTc04, creating a vascular tracer that enhances the quality of electrocardiographically gated imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gated blood pool imaging following 99mTc stannous pyrophosphate imaging. Stokely, EM., Parkey, RW., Bonte, FJ., et al.[2006]

In a study of 36 patients, early technetium-99m pyrophosphate scintigraphy was used to evaluate myocardial preservation after thrombolysis, revealing that strong tracer uptake indicated poorer heart function and larger damage after an acute myocardial infarction.

The findings suggest that a strongly positive scintigraphy result within 12 hours of an acute myocardial infarction may signal inadequate success in reducing heart damage through thrombolysis, highlighting its potential as a predictive tool for treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The scoring system for early technetium-99m pyrophosphate scintigraphy as a method of evaluation of limiting the myocardial infarct size by thrombolysis. Kondo, M., Yuzuki, Y., Shimizu, H., et al.[2019]

In a case study of a patient with severe congestive cardiomyopathy due to myocardial sarcoidosis, various imaging techniques confirmed the diagnosis, including radionuclide ventriculography and scintigraphy with thallium-201 and gallium-67.

For the first time, technetium-99m pyrophosphate (TcPYP) scintigraphy was shown to be as effective as gallium and thallium scans in detecting myocardial involvement in sarcoidosis, highlighting its potential utility in similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radionuclide imaging in myocardial sarcoidosis. Demonstration of myocardial uptake of technetium pyrophosphate99m and gallium. Forman, MB., Sandler, MP., Sacks, GA., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8788016/

99mTechnetium‐pyrophosphate scintigraphy In this review, we discuss the utility of 99m Tc‐labelled bone radiotracer scintigraphy for the early diagnosis of ATTR‐CM based on published literature.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0929664624004819

Use of technetium-99m-pyrophosphate single-photon ... Our results demonstrated a significant decrease in volumetric H/L ratio in hereditary ATTR-CA patients receiving RNA interference therapeutics.

3. jacc.org jacc.org/doi/10.1016/j.jaccao.2024.10.013

Biomarkers to Predict Abnormal Technetium-99m ... Technetium Tc 99m pyrophosphate scintigraphy (99mTc PYP imaging) is a diagnostic tool for transthyretin amyloid cardiomyopathy (ATTR-CM).

4. ahajournals.org ahajournals.org/doi/10.1161/JAHA.123.030512

Use of Technetium‐99m‐Pyrophosphate Single‐Photon ... Eplontersen treatment may be effective in patients with hereditary transthyretin amyloid cardiomyopathy, and technetium‐99m‐pyrophosphate single ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11701493/

2025 Update Consensus of 99mTc-Pyrophosphate ... This updated consensus provides comprehensive guidelines for clinicians, with the aim of optimizing patient outcomes through precise diagnosis and effective ...

6. jamanetwork.com jamanetwork.com/journals/jamacardiology/fullarticle/2546034

Multicenter Study of Planar Technetium 99m ... For 171 patients, Tc 99m PYP cardiac imaging demonstrated 91% sensitivity and 92% specificity for ATTR cardiac amyloidosis.