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

Overview

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.

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Crossover Assignment
  • Primary Purpose: Treatment
  • Masking: Double (Participant, Investigator)
• Study Primary Completion Date: July 1, 2023

Interventions

• Drug: Trimetazidine
  • Oral intake of capsules
• Drug: Placebo
  • Oral intake of capsules

Arms, Groups and Cohorts

• Active Comparator: Active Drug
  • Study participants receiving Trimetazidine
• Placebo Comparator: Placebo
  • Study participants receiving placebo (calcium)

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 60 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Steen Hvitfeldt Poulsen
• Provider of Information About this Clinical Study
  • Sponsor-Investigator: Steen Hvitfeldt Poulsen, Professor, PhD, DMSci – Aarhus University Hospital Skejby
• Overall Contact(s)
  • Bertil T Ladefoged, MD, +4540927245, berlad@rm.dk