Clinical Trial
Study Details
Status
RECRUITING
Study ID #
NCT05374564
Study Start
Primary Completion
Study Completion
Enrollment
12
Study Type
Interventional
Phase
Phase 1
Interventions
(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)

Primary Outcomes
Measure
Determine if ATTR cardiomyopathy disease severity is associated with increased 18F-flutemetamol
Description

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

Timeframe
6 months
Measure
Determine if ATTR cardiomyopathy disease severity is associated with increased 18F-flutemetamol
Description

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

Timeframe
6 months
Measure
Determine if ATTR cardiomyopathy disease severity is associated with increased 18F-flutemetamol
Description

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

Timeframe
6 months
Measure
Determine if ATTR cardiomyopathy disease severity is associated with increased 18F-flutemetamol
Description

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

Timeframe
6 months
Measure
Determine if ATTR cardiomyopathy disease severity is associated with increased 18F-flutemetamol
Description

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

Timeframe
6 months
Measure
Determine if treatment with tafamidis reduces 18F-flutemetamol cardiac PET imaging markers
Description

As assessed by dynamic cardiac PET between baseline and 6 months

Timeframe
6 months
Secondary Outcomes
Measure
Compare changes in 18F-flutemetamol PET variables and measures of ATTR clinical response
Description

As determined by ATTR clinical stage baseline and following 6 months of treatment with tafamidis.

Timeframe
6 months
Measure
Compare changes in 18F-flutemetamol PET variables and measures of ATTR clinical response
Description

As determined by NT-proBNP between baseline and following 6 months of treatment with tafamidis.

Timeframe
6 months
Measure
Compare changes in 18F-flutemetamol PET variables and measures of ATTR clinical response
Description

As determined by TnT between baseline and following 6 months of treatment with tafamidis.

Timeframe
6 months
Measure
Compare changes in 18F-flutemetamol PET variables and measures of ATTR clinical response
Description

As determined by echocardiographic wall thickness between baseline and following 6 months of treatment with tafamidis.

Timeframe
6 months
Measure
Compare changes in 18F-flutemetamol PET variables and measures of ATTR clinical response
Description

As determined by global longitudinal strain between baseline and following 6 months of treatment with tafamidis.

Timeframe
6 months
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.

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).

Conditions
Cardiomyopathies, Primary
Study Contact
Name
Maxime Oriol, BS
Role
Contact
Phone
2037856497
Email
maxime.oriol@yale.edu
Name
Julie Holub
Role
Contact
Email
Julie.holub@yale.edu
Locations
Facility

Yale University
New Haven, CT 06520
United States

Contacts
Study Contact
Name
Edward Miller
Role
Contact
Eligibility Criteria

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.

Eligibility Minimum Age
18 Years
Sexes Eligible for Study
ALL
Eligibility Std Ages
Adult
Older Adult