The Effect of Trimetazidine on Mitochondrial Function, Myocardial Performance, and Invasive Hemodynamics in Patients Diagnosed With Wild-Type Transthyretin Cardiac Amyloidosis

Study Overview
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Brief Summary
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Wild-type transthyretin cardiac amyloidosis (ATTRwt) is a deposition disorder in which one of the proteins of the body misfolds and accumulates at various places in the body, including the heart, leading to both mechanical and cellular damage. The gradual development of the disease will ultimately lead to heart failure and death The protein which deposits in the heart of patients, damages both the heart mechanically as the myocardium becomes rigid and hypertrophic over time but also at the cellular level. Cell damage can be observed by elevated blood tests for cell damage (Troponin) and during exercise tests that show patients' hearts burning oxygen inefficiently when exposed to physical stress compared with the hearts of healthy individuals . No one has, however, intimately studied this cellular damage. Vastarel® (Trimetazidine, TMZ) is an already known drug for the treatment of chest pain. The mechanism of action indicates that it may have an effect on patients with cardiac amyloidosis. The study aims to investigate the effects of TMZ on the mitochondrial function, myocardial performance, and invasive hemodynamics in patients with ATTRwt with a randomized, double-blinded, crossover-trial.

Official Title
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The Effect of Trimetazidine on Mitochondrial Function, Myocardial Performance, and Invasive Hemodynamics in Patients Diagnosed With Wild-Type Transthyretin Cardiac Amyloidosis

Conditions
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Transthyretin Amyloid Cardiopathy, Mitochondrial Pathology

Intervention / Treatment
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* Drug: Trimetazidine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Wild-type transthyretin cardiac amyloidosis NAC stage I NYHA class of I or II Informed consent Exclusion Criteria: Other, similar diagnoses Hereditary transthyretin cardiac amyloidosis Light chain amyloidosis Morbus Waldenstrøm Myelomatosis Medical treatment with loop diuretics in standard doses (40 mgx1 daily) Contraindications to trimetazidine Significant comorbidity assessed by the investigators Unable to provide informed consent

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Drug<br>Study participants receiving Trimetazidine | Drug: Trimetazidine<br>* Oral intake of capsules<br>|
| Placebo Comparator: Placebo<br>Study participants receiving placebo (calcium) | Drug: Placebo<br>* Oral intake of capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change: pulmonary capillary wedge pressure (PCWP) | We hypothesize a change in PCWP of 5 mmHg between the active drug and placebo using right heart catheterization. | Four weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change: cardiac index (CI) | We hypothesize a change in CI of 0.5 L/min between the active drug and placebo using right heart catheterization. | Four weeks of treatment |