E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Wild-Type Transthyretin Cardiac Amyloidosis |
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E.1.1.1 | Medical condition in easily understood language |
Cardiac Amyloidosis |
Hjerteamyloidose |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The purpose of this study is: 1) to characterize the oxidative capacity of myocardial mitochondria as well as to investigate the treatment effect of Trimetazidine (TMZ) in patients with stage 1 cardiac amyloidosis in a double-blind, placebo-controlled cross-over study; 2) to examine the effect of TMZ at rest and during exercise on systolic and diastolic function measured by right heart catheterization (RHC) and advanced echocardiography; 3) to investigate and characterize the morphology of myocardial myocytes and mitochondria by electron microscopy; 4) to compare the oxidative capacity, morphology, and myocardial function of mitochondria in patients with early-stage asymptomatic disease versus patients with more advanced symptomatic disease.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age ≥ 60 years for men. Age ≥ 70 years for women - TC99-DPD-scintigraphy positive for cardiac involvement (Perugini II-III) - Negative serum immunofixation - Normal Kappa/Lambda ratio - Gillmore stage I (NT-proBNP ≤ 3000 ng/L, eGFR ≥ 45 mL/min) - NYHA-class I-IIa - Informed consent
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E.4 | Principal exclusion criteria |
- Already known, similar diagnosis o Hereditary Transthyretin Cardiac Amyloidosis (ATTRh) o Light Chain Amyloidosis (AL Amyloidosis) o Monoclonal Gammopathy of Unspecified Significance (MGUS) o Myelomatosis o Mb. Waldenstrøm - Medical treatment with loop diuretics - Contraindications to TMZ (Allergic reaction, Parkinson’s Disease, Tremor, Restless Leg Syndrome, eGFR < 30 mL/min) - Contraindications to TC99-DPD-skintigraphy (allergic reaction to contrast) - Significant co-morbidity assessed by the investigator - Patients for whom informed consent cannot be collected (mental illness, dementia)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point is cardiac index measured by RHC.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary end points are mitochondrial respiration measured by high resolution respirometry, left ventricular global longitudinal strain measured by transthoracic echocardiography, and walking distance on the 6-minute walk test. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of last subject undergoing the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |