Imaging heart fibrosis in patients with cardiac amyloidosis

Molecular Imaging of Myocardial Fibrosis in Cardiac Amyloidosis

This study is testing a new imaging tool to see if it can help measure heart scarring in people with cardiac amyloidosis and compare it to other heart conditions.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 65 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Brigham and Women's Hospital (Academic / other)
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT05619302 on ClinicalTrials.gov

What this trial studies

This pilot study aims to evaluate the effectiveness of a novel PET probe, [68Ga]CBP8, in measuring myocardial fibrosis in patients diagnosed with cardiac amyloidosis. The study will involve 30 individuals with cardiac amyloidosis, alongside control groups including patients with myocardial infarction, hypertrophic cardiomyopathy, and healthy individuals. The primary hypothesis is that [68Ga]CBP8 will bind to collagen in the heart, allowing for quantification of fibrosis, which may help in understanding the severity of the condition and guiding treatment decisions. The study will utilize advanced imaging techniques, including PET and MRI, to assess the uptake of the probe in different patient groups.

Who should consider this trial

Good fit: Ideal candidates for this study are adults over 18 years old with a confirmed diagnosis of systemic light chain amyloidosis and evidence of cardiac involvement.

Not a fit: Patients without cardiac amyloidosis or those with other forms of heart disease not related to amyloidosis may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new method for accurately diagnosing and quantifying myocardial fibrosis in patients with cardiac amyloidosis, potentially leading to better-targeted therapies.

How similar studies have performed: While the use of [68Ga]CBP8 in humans is relatively novel, preliminary studies in other fibrotic conditions have shown promising results, suggesting potential for success in this application.

Eligibility criteria

Inclusion Criteria for AL-amyloid subjects:

* Age \> 18 years
* Willing and able to provide consent
* AL-CA: Diagnosis of systemic light chain amyloidosis by standard criteria: Immunofixation of serum, serum free light chain (FLC) assay, a biopsy of fat pad/bone marrow, or organ biopsy, followed by typing of the light chain using immunohistochemistry or immunogold assay with confirmation by mass spectroscopy as needed AND

  * Proof of cardiac involvement by AL amyloidosis
  * Abnormal cardiac biomarkers: abnormal high sensitivity TnT 5th generation levels (\> 15 ng/L) or abnormal age-appropriate NT-proBNP (abnormal values: \< 50 years: \> 450 pg/ml; 50-75 years: \> 900 pg/ml; \> 75 years: \> 1800 pg/ml) OR
  * Abnormal echocardiogram (wall thickness \> 12 mm in the absence of other causes of increased LV wall thickness) OR
  * Abnormal CMR (wall thickness \> 12 mm, extracellular volume \> 0.40 or typical CMR appearance of cardiac amyloidosis with difficulty nulling images and non-coronary distribution late gadolinium enhancement) OR
  * Positive endomyocardial biopsy

Inclusion Criteria for ATTR-amyloid subjects:

* Age \> 18 years
* Willing and able to provide consent
* ATTR-CA: Diagnosis of either wildtype or hereditary transthyretin cardiac amyloidosis by standard criteria: Endomyocardial biopsy followed by typing of the transthyretin amyloidosis using immunohistochemistry or immunogold assay with confirmation by mass spectroscopy as needed

  * Extracardiac biopsy with typical cardiac imaging findings
  * Hereditary ATTR amyloidosis by genetic testing OR
  * Grade 2 or grade 3 myocardial uptake of 99mTc-PYP if AL amyloidosis is excluded

Inclusion Criteria for recent myocardial infarction subjects:

* Age \> 18 years
* Willing and able to provide consent
* Recent MI: Diagnosis of recent type 1 myocardial infarction by standard criteria

  * More than 6 weeks from diagnosis of MI but within 6 months
  * Imaging evidence of loss of viable myocardium or persistent regional wall motion abnormalities in a pattern consistent with an ischemic etiology in more than one segment

Inclusion Criteria for hypertrophic cardiomyopathy subjects:

* Age \> 18 years
* Willing and able to provide consent
* Hypertrophic cardiomyopathy: Diagnosis of hypertrophic cardiomyopathy by standard criteria
* MRI evidence of late gadolinium enhancement

Inclusion Criteria for recent healthy control subjects:

* Age \> 18 years
* Willing and able to provide consent
* No known cardiac amyloidosis or recent myocardial infarction

Exclusion Criteria:

* Dialysis
* NYHA (New York Heart Association) Class IV
* Acute myocardial infarction within 6 weeks
* Pregnancy or nursing
* History of adverse events from or allergy to gadolinium contrast media
* Hemodynamic instability
* Severe claustrophobia despite use of sedatives
* Decompensated heart failure (unable to lie flat for 1 hour)
* Concomitant clinically significant non-ischemic non-amyloid heart disease (valvular heart disease or dilated cardiomyopathy)
* Body weight over limit for MRI table (\>300 lbs)
* Contraindications for MRI (including non-compatible cardiac implantable electronic devices, drug infusion pumps, and metallic or electric implants)
* Any other reason determined by the investigator to be unsuitable for the study

Where this trial is running

Boston, Massachusetts

• Brigham and Women's Hospital — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Principal investigator: Sharmila Dorbala, MD — Brigham and Women's Hospital
• Study coordinator: Vaidehi Chemburkar, MS

Conditions Cardiac Amyloidosis; Amyloidosis; Cardiac; Heart; Imaging; Diagnosis