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

NCT05633563 | Completed Phase 4

• 1 other identifier: 72864
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Transthyretin Amyloid Cardiopathy; Mitochondrial Pathology

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Change: cardiac index (CI)

  Four weeks of treatment

Study Arms (2)

Active Drug

ACTIVE COMPARATOR

Study participants receiving Trimetazidine

Drug: Trimetazidine

Placebo

PLACEBO COMPARATOR

Study participants receiving placebo (calcium)

Drug: Placebo

Interventions

Trimetazidine DRUG

Oral intake of capsules

Active Drug

Placebo DRUG

Oral intake of capsules

Placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Wild-type transthyretin cardiac amyloidosis
• NAC stage I
• NYHA class of I or II
• Informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Steen Hvitfeldt Poulsen: lead

Study Sites (1)

Aarhus University Hospital, Department of Cardiology

Aarhus N, Danmark, 8200, Denmark

Location

MeSH Terms

Interventions

Trimetazidine

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, PhD, DMSci

Study Record Dates

• First Submitted: October 15, 2021
• First Posted: December 1, 2022
• Study Start: October 1, 2021
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2023
• Last Updated: April 25, 2024

Record last verified: 2024-04

Locations

DK (1)