Parametric Cardiac 18F-flutemetamol PET Imaging in ATTR Cardiomyopathy

Study Overview
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Brief Summary
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18F-Flutemetamol (Vizamyl) is a radioactive diagnostic agent indicated and FDA-approved for Positron Emission Tomography (PET) imaging of the brain to estimate β-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease (AD) or other causes of cognitive decline. This study is designed to evaluate a novel use for 18F-Flutemetamol in cardiac amyloidosis.

Detailed Description
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The goal of this project is to perform a proof-of-concept study to compare the ability of quantitative parametric cardiac 18F-flutemetamol positron emission tomography (PET) to assess baseline and change in disease burden after six months of therapy with tafamidis treatment in 12 patients diagnosed with transthyretin cardiac amyloidosis (ATTR-CA) at Yale-New Haven Hospital. The primary outcome of the study will be comparisons in the magnitude of change in regional and global 18F-flutemetamol cardiac PET metrics between the baseline and six-month 18F-flutemetamol PET scans versus clinical stage and echocardiographic features (wall thickness, strain, LVEF).

Official Title
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Parametric Cardiac 18F-flutemetamol PET Imaging in ATTR Cardiomyopathy

Conditions
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Cardiomyopathies, Primary

Intervention / Treatment
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* Drug: (18F)Flutemetamol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Age > 18 years 2. Diagnosis of ATTR cardiac amyloidosis (wild-type or V142I ATTR mutation) a. Diagnosis of ATTR cardiac amyloidosis by established consensus diagnostic criteria of Gillmore et al. (either invasive or non-invasive diagnostic pathways) 3. Plan for initiation of tafamidis therapy for clinical indications and agree to continue tafamidis during the duration of the study. 4. Stated willingness to comply with all study procedures and availability for the duration of the study 5. Able to understand and sign the informed consent document after the nature of the study has been fully explained. 6. Women of childbearing potential who are sexually active with a non-sterilized male partner and males who are sexually active with a partner of childbearing potential must agree to use adequate contraception from screening until 30 days after the Flutemetamol. Exclusion Criteria: 1. Primary amyloidosis (AL) or secondary amyloidosis (AA). 2. Prior liver or heart transplantation. 3. Active malignancy or non-amyloid disease with an expected survival of less than 1 year 4. Inability to lie flat for 60 minutes in the PET scanner 5. History of prior treatment for ATTR cardiomyopathy and/or amyloid neuropathy, or decline clinical tafamidis treatment. 6. Pregnancy or lactation 7. Known allergic reactions to components of the 18F-flutemetamol and/or polysorbate 80 8. High risk for non-adherence as determined by screening evaluation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: The proposed study will be a single-arm open-label longitudinal study of 18F-flutemetamol cardiac imaging before/after six months of tafamidis treatment in 12 patients with treatment naïve ATTR cardiac amyloidosis.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 18F-flutemetamol<br>All clinical trial subjects will receive 18F-flutemetamol | Drug: (18F)Flutemetamol<br>* 18F-Flutemetamol binds to β-amyloid plaques and the F-18 isotope produces a positron signal that is detected by a PET scanner. Multiple recent studies have shown that thioflavin-analogue tracers such as 18F-flutemetamol may be able to fulfill the unmet need of elucidating the presence of amyloid deposition in the heart. Because it binds to the beta-pleated motif of the amyloid fibril due to their similarity to the thioflavin structure, 18F-Flutemetamol could potentially be used to image cardiac amyloidosis (CA)<br>* Other names: Vizamyl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine if ATTR cardiomyopathy disease severity is associated with increased 18F-flutemetamol | As determined by comparisons in the magnitude of change in regional and global 18F-flutemetamol cardiac PET visual uptake scores between the baseline and six-month PET scans | 6 months | 
| Determine if ATTR cardiomyopathy disease severity is associated with increased 18F-flutemetamol | As determined by comparisons in the magnitude of change in regional and global 18F-flutemetamol cardiac PET percent maximal counts between the baseline and six-month PET scans | 6 months | 
| Determine if ATTR cardiomyopathy disease severity is associated with increased 18F-flutemetamol | As determined by comparisons in the magnitude of change in regional and global 18F-flutemetamol cardiac PET Standardized Uptake Values (SUVs) between the baseline and six-month PET scans | 6 months | 
| Determine if ATTR cardiomyopathy disease severity is associated with increased 18F-flutemetamol | As determined by comparisons in the magnitude of change in regional and global 18F-flutemetamol cardiac PET retention index between the baseline and six-month PET scans | 6 months | 
| Determine if ATTR cardiomyopathy disease severity is associated with increased 18F-flutemetamol | As determined by comparisons in the magnitude of change in regional and global 18F-flutemetamol cardiac PET Vt between the baseline and six-month PET scans | 6 months | 
| Determine if treatment with tafamidis reduces 18F-flutemetamol cardiac PET imaging markers | As assessed by dynamic cardiac PET between baseline and 6 months | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare changes in 18F-flutemetamol PET variables and measures of ATTR clinical response | As determined by ATTR clinical stage baseline and following 6 months of treatment with tafamidis. | 6 months | 
| Compare changes in 18F-flutemetamol PET variables and measures of ATTR clinical response | As determined by NT-proBNP between baseline and following 6 months of treatment with tafamidis. | 6 months | 
| Compare changes in 18F-flutemetamol PET variables and measures of ATTR clinical response | As determined by TnT between baseline and following 6 months of treatment with tafamidis. | 6 months | 
| Compare changes in 18F-flutemetamol PET variables and measures of ATTR clinical response | As determined by echocardiographic wall thickness between baseline and following 6 months of treatment with tafamidis. | 6 months | 
| Compare changes in 18F-flutemetamol PET variables and measures of ATTR clinical response | As determined by global longitudinal strain between baseline and following 6 months of treatment with tafamidis. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transthyretin amyloidosis