Amyloidosis TTR Flow Reserve Evaluation

NCT ID: NCT05103943

Last Updated: 2025-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-24

Study Completion Date

2026-12-11

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Amyloid Cardiomyopathy

Keywords

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Tafamidis

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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SPECT MPI (myocardial perfusion imaging) Group

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.

Group Type EXPERIMENTAL

SPECT MPI

Intervention Type OTHER

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

Interventions

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SPECT MPI

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

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Centre Hospitalier Régional d'Orléans

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Matthieu BAILLY, Dr

Role: PRINCIPAL_INVESTIGATOR

CHU Orléans

Locations

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CHU d'ANGERS

Angers, , France

Site Status

CHU Caen

Caen, , France

Site Status

CHU Orleans

Orléans, , France

Site Status

CHRU de TOURS

Tours, , France

Site Status

Countries

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France

References

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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.

Reference Type BACKGROUND
PMID: 25023822 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30145929 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10610629 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11330510 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15310723 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27081447 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36082269 (View on PubMed)

Other Identifiers

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CHRO-2021-05

Identifier Type: -

Identifier Source: org_study_id