Evaluation of the Effect of Trimetazidine on Coronary Flow in Transthyretin Cardiac Amyloidosis
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Change in Coronary Flow Reserve
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Trimetazidine
Trimetazidine 35 mg twice daily for 6 months. Participants with an estimated glomerular filtration rate between 30 and 60 mL/min/1.73 m² will receive 35 mg once daily.
干预措施: Trimetazidine (Drug)
结局指标
主要结局
Change in Coronary Flow Reserve
时间窗: Baseline to approximately 6 months
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.
次要结局
- Change in 6-Minute Walk Distance(Baseline to approximately 6 months)
- Change in NT-proBNP(Baseline to approximately 6 months)
- Change in Kansas City Cardiomyopathy Questionnaire Score(Baseline to approximately 6 months)
研究者
Fábio Fernandes
Collaborating Professor, Department of Cardiopneumology, University of São Paulo Medical School
University of Sao Paulo General Hospital