Amyloidosis TTR Flow Reserve Evaluation

Amyloid Cardiomyopathy Clinical Trial

— AMYTRE  

Official title:

Amyloidosis TTR Flow Reserve Evaluation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05103943
• Other study ID #: CHRO-2021-05
• Status: Recruiting
• Phase: N/A
• Start date: February 24, 2022
• Est. completion date: February 2026

Study information

• Verified date: July 2023
• Source: Centre Hospitalier Régional d'Orléans
• Contact: Aurélie DESPUJOLS
• Phone: +33238744071
• Email: aurelie.despujols[@]chr-orleans.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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:

1. to confirm the results of Dorbala et al using SPECT, and

2. to go further with evaluation of the effect of Tafamidis on microvascular dysfunction.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: February 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Amyloid Cardiomyopathy
• Amyloidosis
• Cardiomyopathies

Intervention

Other:
• SPECT MPI
SPECT MPI including dynamic acquisitions for stress, rest MBF and MFR

Locations

Country	Name	City	State
France	CHU d'ANGERS	Angers
France	CHR d'Orleans	Orléans
France	CHRU de TOURS	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Régional d'Orléans

Country where clinical trial is conducted

France, 

References & Publications (6)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Month 24
Primary	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)	Month 24
Secondary	Number or participants with stress reduction	Stress assessed by dynamic SPECT (regional and global left ventricle measurements), in comparison to "normal" values	baseline
Secondary	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	baseline
Secondary	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	Baseline