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Parametric Cardiac 18F-flutemetamol PET Imaging in ATTR Cardiomyopathy

Primary Purpose

Cardiomyopathies, Primary

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

(18F)Flutemetamol

About this trial

This is an interventional treatment trial for Cardiomyopathies, Primary focused on measuring Transthyretin amyloidosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Yale UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

18F-flutemetamol

Arm Description

All clinical trial subjects will receive 18F-flutemetamol

Outcomes

Primary Outcome Measures

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

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

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

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

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

Determine if treatment with tafamidis reduces 18F-flutemetamol cardiac PET imaging markers

As assessed by dynamic cardiac PET between baseline and 6 months

Secondary Outcome Measures

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT05374564

First Posted

May 10, 2022

Last Updated

August 9, 2023

Sponsor

Yale University

Collaborators

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT05374564

Brief Title

Parametric Cardiac 18F-flutemetamol PET Imaging in ATTR Cardiomyopathy

Official Title

Parametric Cardiac 18F-flutemetamol PET Imaging in ATTR Cardiomyopathy

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 16, 2022 (Actual)

Primary Completion Date

June 2024 (Anticipated)

Study Completion Date

September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Yale University

Collaborators

Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cardiomyopathies, Primary

Keywords

Transthyretin amyloidosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

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)

Allocation

N/A

Enrollment

12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

18F-flutemetamol

Arm Type

Experimental

Arm Description

All clinical trial subjects will receive 18F-flutemetamol

Intervention Type

Drug

Intervention Name(s)

(18F)Flutemetamol

Other Intervention Name(s)

Vizamyl

Intervention Description

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 Outcome Measure Information:

Title

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

Time Frame

6 months

Title

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

Time Frame

6 months

Title

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

Time Frame

6 months

Title

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

Time Frame

6 months

Title

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

Time Frame

6 months

Title

Determine if treatment with tafamidis reduces 18F-flutemetamol cardiac PET imaging markers

Description

As assessed by dynamic cardiac PET between baseline and 6 months

Time Frame

6 months

Secondary Outcome Measure Information:

Title

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.

Time Frame

6 months

Title

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.

Time Frame

6 months

Title

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.

Time Frame

6 months

Title

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.

Time Frame

6 months

Title

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.

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Maxime Oriol, BS

Phone

2037856497

maxime.oriol@yale.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Julie Holub

Julie.holub@yale.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Edward J Miller, MD

Organizational Affiliation

Yale University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Yale University

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06520

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Edward Miller

12. IPD Sharing Statement

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Parametric Cardiac 18F-flutemetamol PET Imaging in ATTR Cardiomyopathy

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