Cardiomyopathies, Primary
Conditions
Keywords
Transthyretin amyloidosis
Brief summary
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
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).
Interventions
DRUG(18F)Flutemetamol
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)
Sponsors
Pfizer
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine if ATTR cardiomyopathy disease severity is associated with increased 18F-flutemetamol | 6 months | 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 |
| Determine if treatment with tafamidis reduces 18F-flutemetamol cardiac PET imaging markers | 6 months | As assessed by dynamic cardiac PET between baseline and 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare changes in 18F-flutemetamol PET variables and measures of ATTR clinical response | 6 months | As determined by ATTR clinical stage baseline and following 6 months of treatment with tafamidis. |
Countries
United States
Outcome results
None listed