Effect of Trimetazidine on Coronary Flow in Transthyretin Cardiac Amyloidosis

Phase 2Not Yet RecruitingNCT07836699

Fábio Fernandes20 enrolled

Overview

The goal of this clinical trial is to learn if trimetazidine can improve blood flow in the heart in adults with transthyretin cardiac amyloidosis (ATTR-CM). ATTR-CM is a condition in which an abnormal protein builds up in the heart and can make it harder for the heart to work normally. The main question this study aims to answer is: Does trimetazidine improve the heart's ability to increase its blood flow when more blood is needed? The study will also look at whether treatment is linked to changes in walking ability, heart-related blood tests, heart function, and quality of life. Participants will: Take trimetazidine for about 6 months. Have heart blood flow measured with a positron emission tomography/computed tomography (PET/CT) scan before and after treatment. Have heart ultrasound examinations and blood tests. Complete a 6-minute walk test and a questionnaire about their symptoms and quality of life.

Transthyretin cardiac amyloidosis (ATTR-CM) is characterized by the deposition of transthyretin amyloid fibrils within the myocardium. In addition to myocardial infiltration, amyloid deposition may involve intramyocardial vessels and contribute to coronary microvascular dysfunction. This may lead to impaired myocardial perfusion and reduced coronary flow reserve even in the absence of significant obstructive epicardial coronary artery disease. Trimetazidine is a metabolic modulator that shifts myocardial energy metabolism from fatty acid oxidation toward glucose oxidation. This metabolic effect may improve myocardial energy efficiency and reduce oxygen requirements for adenosine triphosphate production. These properties provide the rationale for investigating whether trimetazidine may improve coronary microvascular function in people with ATTR-CM. TACT-TTR is a prospective, open-label, single-center, single-arm pilot clinical trial conducted at the Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (InCor-HCFMUSP). The study will enroll 20 participants with ATTR-CM who will receive trimetazidine and undergo approximately 6 months of follow-up. Coronary physiology will be assessed using quantitative myocardial perfusion imaging with nitrogen-13 ammonia positron emission tomography/computed tomography (PET/CT). Myocardial blood flow will be measured at rest and during pharmacologic stress, allowing calculation of coronary flow reserve as the ratio of stress myocardial blood flow to resting myocardial blood flow. Participants will undergo assessments before and after the treatment period to investigate changes in coronary microvascular function. Additional clinical, imaging, laboratory, functional, and health-related quality-of-life assessments will be performed during follow-up. This exploratory pilot study is intended to provide preliminary evidence on the potential role of trimetazidine as an adjunctive metabolic therapy targeting coronary microvascular dysfunction in ATTR-CM and to generate data that may support the design of future controlled clinical trials.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Diagnosis of transthyretin cardiac amyloidosis confirmed by all protocol-specified diagnostic criteria or by Congo red-positive tissue biopsy with cardiac involvement. The diagnostic criteria listed in the current protocol include: * Interventricular septal thickness \>12 mm on echocardiography or cardiac magnetic resonance imaging, in the absence of other causes of hypertrophy (e.g., hypertension or aortic stenosis) * History of signs or symptoms of heart failure consistent with cardiac amyloidosis * Cardiac scintigraphy with technetium-99m pyrophosphate showing grade II or III uptake according to the Perugini scale * Age \>18 years * New York Heart Association (NYHA) functional class II, III, or IV Exclusion Criteria: * Previous adverse reaction, intolerance, or other contraindication to trimetazidine * Serum kappa/lambda ratio outside the normal range * Use of calcium channel blockers, beta-blockers, or nitrates * Obstructive coronary artery disease, defined as \>50% stenosis in any major epicardial coronary artery, demonstrated by coronary computed tomography angiography * Active infection, inflammatory disease, or other systemic condition that may affect myocardial perfusion * Contraindication to dipyridamole or PET/CT imaging * Estimated glomerular filtration rate \<30 mL/min/1.73 m², calculated using the CKD-EPI equation * Pregnancy or postpartum period * Presence of diseases other than cardiac amyloidosis that may impair functional capacity or limit ambulation during the 6-minute walk test * Other medical conditions or comorbidities that, in the investigator's opinion, may interfere with the course of the study or interpretation of the data * Refusal to provide written informed consent

Outcomes

Primary Outcomes

Change in Coronary Flow Reserve

Coronary flow reserve (CFR) will be measured using nitrogen-13 ammonia PET/CT. CFR is calculated as the ratio of myocardial blood flow during pharmacologic stress to myocardial blood flow at rest. The outcome will assess the change in CFR from baseline to the end of trimetazidine treatment.

Time frame: Baseline to approximately 6 months

Secondary Outcomes

Change in 6-Minute Walk Distance

Change in distance walked during the 6-minute walk test from baseline to approximately 6 months. A gain of 30 meters or more will be assessed as a clinically relevant improvement.

Time frame: Baseline to approximately 6 months

Change in NT-proBNP

Change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration from baseline to approximately 6 months. The study will assess whether NT-proBNP decreases by 30% or more from baseline.

Time frame: Baseline to approximately 6 months

Change in Kansas City Cardiomyopathy Questionnaire Score

Change in heart failure-related health status and quality of life measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ) from baseline to approximately 6 months. Higher scores indicate better health status.

Time frame: Baseline to approximately 6 months

Effect of Trimetazidine on Coronary Flow in Transthyretin Cardiac Amyloidosis

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts