search
Back to results

Amyloidosis TTR Flow Reserve Evaluation (AMYTRE)

Primary Purpose

Amyloid Cardiomyopathy

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
SPECT MPI
Sponsored by
Centre Hospitalier Régional d'Orléans
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Amyloid Cardiomyopathy focused on measuring Tafamidis

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients aged from 18 to 90 years
  • Understanding and speaking French
  • With TTR amyloid cardiomyopathy (ATTRxt or ATTRm) confirmed by the association of heart failure, syncope or bradyarrhythmia, with electrocardiogram and/or magnetic resonance imaging (CMR) suggesting/indicating cardiac amyloid, grade 2 or 3 99mTc- PYP or bone scintigraphy and negative biological findings (i.e. serum immunofixation, urine immunofixation, serum free light chain assay); or, if one of those criteria is not met, presence of amyloid deposits on analysis of biopsy specimens obtained from cardiac and non-cardiac sites (17-19),
  • Intention to treat (Tafamidis)

Exclusion Criteria:

  • Heart failure not due to transthyretin amyloid cardiomyopathy;
  • New York Heart Association (NYHA) class IV heart failure.
  • The presence of light-chain amyloidosis;
  • A history of liver or heart transplantation;
  • An estimated glomerular filtration rate lower than 25 mL per minute per 1.73 m2 of bodysurface area (Cockcroft).
  • Liver transaminase levels exceeding two times the upper limit of the normal range;
  • Severe malnutrition as defined by a modified body-mass index (mBMI) of less than 600, calculated as the serum albumin level in grams per litter multiplied by the conventional BMI (the weight in kilograms divided by the square of the height in meters);
  • Patients receiving concurrent treatment with nonsteroidal anti-inflammatory drugs, tauroursodeoxycholate, doxycycline, calcium-channel blockers, or digitalis;
  • Previous treatment with tafamidis or patisaran;
  • Ticagrelor treatment
  • Previous CAD, severe epicardial stenosis with revascularization or ticagrelor treatment, coronary artery bypass grafting, myocardial infarction;
  • Contra-indications to pharmacological stress testing MPI: severe hypotension (< 90 mmHg of Systolic arterial pressure), atrioventricular block 2nd or 3rd grade, carotid stenosis (unilateral >70%, bilateral >50%);
  • Pregnancy
  • Breastfeeding
  • Protected adults
  • Other study participation

Sites / Locations

  • CHU d'ANGERSRecruiting
  • CHR d'OrleansRecruiting
  • CHRU de TOURSRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SPECT MPI (myocardial perfusion imaging) Group

Arm Description

the SPECT MPI protocol will be modified to evaluated MBF and MFR. This modification will result in no added radiation; the radiopharmaceutical dose will still be the same compared to a standard MPI protocol.

Outcomes

Primary Outcome Measures

Difference of Stress and Rest Myocardial Blood Flow
Difference of Stress and Rest Myocardial Blood Flow (mL/min/g) at baseline and after 24 months of treatments, assessed by dynamic SPECT (regional and global left ventricle measurements)
ratio of Stress Myocardial Blood Flow/ Rest Myocardial Blood Flow
Difference of Myocardial Flow Reserve (ie ratio of Stress Myocardial Blood Flow/ Rest Myocardial Blood Flow) at baseline and after 24 months of treatments, assessed by dynamic SPECT (regional and global left ventricle measurements)

Secondary Outcome Measures

Number or participants with stress reduction
Stress assessed by dynamic SPECT (regional and global left ventricle measurements), in comparison to "normal" values
Number or participants with rest MBF (myocardial blood flow) reduction
Rest Myocardial Blood Flow (mL/min/g) assessed by dynamic SPECT (regional and global left ventricle measurements), in comparison to "normal" values
ratio of Stress Myocardial Blood Flow/ Rest Myocardial Blood Flow
Myocardial Flow Reserve (ie ratio of Stress Myocardial Blood Flow/ Rest Myocardial Blood Flow) assessed by dynamic SPECT (regional and global left ventricle measurements) in comparison to "normal" values

Full Information

First Posted
September 30, 2021
Last Updated
July 19, 2023
Sponsor
Centre Hospitalier Régional d'Orléans
search

1. Study Identification

Unique Protocol Identification Number
NCT05103943
Brief Title
Amyloidosis TTR Flow Reserve Evaluation
Acronym
AMYTRE
Official Title
Amyloidosis TTR Flow Reserve Evaluation
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 24, 2022 (Actual)
Primary Completion Date
February 2026 (Anticipated)
Study Completion Date
February 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Régional d'Orléans

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Anginal symptoms and signs of ischemia have been reported in some patients with cardiac amyloidosis (TTR) without obstructive epicardial coronary artery disease (CAD). It was found that coronary microvascular dysfunction was highly prevalent in subjects with cardiac amyloidosis, even in the absence of epicardial CAD. The investigators found lower stress and rest myocardial blood flow (MBF) and lower myocardial flow reserve (MFR) in their cardiac PET (Positron emission tomography) study (13N), including 21 patients. The advances in SPECT technology including cadmium zinc telluride (CZT) detectors allow to evaluate the MBF and MFR estimation by SPECT as shown in both experimental animal models and also in clinical studies with comparison to PET. SPECT is more widely available than cardiac PET. Thus, the investigators would like: to confirm the results of Dorbala et al using SPECT, and to go further with evaluation of the effect of Tafamidis on microvascular dysfunction.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyloid Cardiomyopathy
Keywords
Tafamidis

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SPECT MPI (myocardial perfusion imaging) Group
Arm Type
Experimental
Arm Description
the SPECT MPI protocol will be modified to evaluated MBF and MFR. This modification will result in no added radiation; the radiopharmaceutical dose will still be the same compared to a standard MPI protocol.
Intervention Type
Other
Intervention Name(s)
SPECT MPI
Intervention Description
SPECT MPI including dynamic acquisitions for stress, rest MBF and MFR
Primary Outcome Measure Information:
Title
Difference of Stress and Rest Myocardial Blood Flow
Description
Difference of Stress and Rest Myocardial Blood Flow (mL/min/g) at baseline and after 24 months of treatments, assessed by dynamic SPECT (regional and global left ventricle measurements)
Time Frame
Month 24
Title
ratio of Stress Myocardial Blood Flow/ Rest Myocardial Blood Flow
Description
Difference of Myocardial Flow Reserve (ie ratio of Stress Myocardial Blood Flow/ Rest Myocardial Blood Flow) at baseline and after 24 months of treatments, assessed by dynamic SPECT (regional and global left ventricle measurements)
Time Frame
Month 24
Secondary Outcome Measure Information:
Title
Number or participants with stress reduction
Description
Stress assessed by dynamic SPECT (regional and global left ventricle measurements), in comparison to "normal" values
Time Frame
baseline
Title
Number or participants with rest MBF (myocardial blood flow) reduction
Description
Rest Myocardial Blood Flow (mL/min/g) assessed by dynamic SPECT (regional and global left ventricle measurements), in comparison to "normal" values
Time Frame
baseline
Title
ratio of Stress Myocardial Blood Flow/ Rest Myocardial Blood Flow
Description
Myocardial Flow Reserve (ie ratio of Stress Myocardial Blood Flow/ Rest Myocardial Blood Flow) assessed by dynamic SPECT (regional and global left ventricle measurements) in comparison to "normal" values
Time Frame
Baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients aged from 18 to 90 years Understanding and speaking French With TTR amyloid cardiomyopathy (ATTRxt or ATTRm) confirmed by the association of heart failure, syncope or bradyarrhythmia, with electrocardiogram and/or magnetic resonance imaging (CMR) suggesting/indicating cardiac amyloid, grade 2 or 3 99mTc- PYP or bone scintigraphy and negative biological findings (i.e. serum immunofixation, urine immunofixation, serum free light chain assay); or, if one of those criteria is not met, presence of amyloid deposits on analysis of biopsy specimens obtained from cardiac and non-cardiac sites (17-19), Intention to treat (Tafamidis) Exclusion Criteria: Heart failure not due to transthyretin amyloid cardiomyopathy; New York Heart Association (NYHA) class IV heart failure. The presence of light-chain amyloidosis; A history of liver or heart transplantation; An estimated glomerular filtration rate lower than 25 mL per minute per 1.73 m2 of bodysurface area (Cockcroft). Liver transaminase levels exceeding two times the upper limit of the normal range; Severe malnutrition as defined by a modified body-mass index (mBMI) of less than 600, calculated as the serum albumin level in grams per litter multiplied by the conventional BMI (the weight in kilograms divided by the square of the height in meters); Patients receiving concurrent treatment with nonsteroidal anti-inflammatory drugs, tauroursodeoxycholate, doxycycline, calcium-channel blockers, or digitalis; Previous treatment with tafamidis or patisaran; Ticagrelor treatment Previous CAD, severe epicardial stenosis with revascularization or ticagrelor treatment, coronary artery bypass grafting, myocardial infarction; Contra-indications to pharmacological stress testing MPI: severe hypotension (< 90 mmHg of Systolic arterial pressure), atrioventricular block 2nd or 3rd grade, carotid stenosis (unilateral >70%, bilateral >50%); Pregnancy Breastfeeding Protected adults Other study participation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Aurélie DESPUJOLS
Phone
+33238744071
Email
aurelie.despujols@chr-orleans.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthieu BAILLY, Dr
Organizational Affiliation
CHR d'ORLEANS
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU d'ANGERS
City
Angers
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Loïc BIERRE, Dr
Facility Name
CHR d'Orleans
City
Orléans
ZIP/Postal Code
45067
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthieu BAILLY, Dr
Email
matthieu.bailly@chr-orleans.fr
Facility Name
CHRU de TOURS
City
Tours
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne BERNARD, Pr

12. IPD Sharing Statement

Citations:
PubMed Identifier
25023822
Citation
Dorbala S, Vangala D, Bruyere J Jr, Quarta C, Kruger J, Padera R, Foster C, Hanley M, Di Carli MF, Falk R. Coronary microvascular dysfunction is related to abnormalities in myocardial structure and function in cardiac amyloidosis. JACC Heart Fail. 2014 Aug;2(4):358-67. doi: 10.1016/j.jchf.2014.03.009. Epub 2014 Jul 9.
Results Reference
background
PubMed Identifier
30145929
Citation
Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, Kristen AV, Grogan M, Witteles R, Damy T, Drachman BM, Shah SJ, Hanna M, Judge DP, Barsdorf AI, Huber P, Patterson TA, Riley S, Schumacher J, Stewart M, Sultan MB, Rapezzi C; ATTR-ACT Study Investigators. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018 Sep 13;379(11):1007-1016. doi: 10.1056/NEJMoa1805689. Epub 2018 Aug 27.
Results Reference
background
PubMed Identifier
10610629
Citation
Al Suwaidi J, Velianou JL, Gertz MA, Cannon RO 3rd, Higano ST, Holmes DR Jr, Lerman A. Systemic amyloidosis presenting with angina pectoris. Ann Intern Med. 1999 Dec 7;131(11):838-41. doi: 10.7326/0003-4819-131-11-199912070-00007.
Results Reference
background
PubMed Identifier
11330510
Citation
Ogawa H, Mizuno Y, Ohkawara S, Tsujita K, Ando Y, Yoshinaga M, Yasue H. Cardiac amyloidosis presenting as microvascular angina--a case report. Angiology. 2001 Apr;52(4):273-8. doi: 10.1177/000331970105200407.
Results Reference
background
PubMed Identifier
15310723
Citation
Whitaker DC, Tungekar MF, Dussek JE. Angina with a normal coronary angiogram caused by amyloidosis. Heart. 2004 Sep;90(9):e54. doi: 10.1136/hrt.2004.038984.
Results Reference
background
PubMed Identifier
27081447
Citation
Nam MC, Nel K, Senior R, Greaves K. Abnormal Myocardial Blood Flow Reserve Observed in Cardiac Amyloidosis. J Cardiovasc Ultrasound. 2016 Mar;24(1):64-7. doi: 10.4250/jcu.2016.24.1.64. Epub 2016 Mar 24.
Results Reference
background
PubMed Identifier
36082269
Citation
Vancon B, Bisson A, Courtehoux M, Bernard A, Bailly M. A study protocol for an observational cohort investigating cardiac transthyretin amyloidosis flow reserve before and after Tafamidis treatment: The AMYTRE study. Front Med (Lausanne). 2022 Aug 23;9:978293. doi: 10.3389/fmed.2022.978293. eCollection 2022.
Results Reference
derived

Learn more about this trial

Amyloidosis TTR Flow Reserve Evaluation

We'll reach out to this number within 24 hrs