MEK Inhibitors for the Treatment of Hypertrophic Cardiomyopathy in Patients With RASopathies

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-08-01

Study Completion Date

2026-12-01

Brief Summary

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The goal of this study is to evaluate the effectiveness of trametinib treatment in patients with Hyperthropic cardiomyopathy and a genetic mutation in the RAS/MAPK pathway.

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Detailed Description

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Introduction RASopathies are a group of genetic diseases caused by mutations in the mitogen-activated kinase (RAS-MAPK) pathway. These mutations affect many processes and are the cause of numerous genetic syndromes (including Noonan syndrome) in the course of which severe hypertrophic cardiomyopathy (HCM) develops. MEK kinase inhibitors are used to treat cancers with mutations in the RAS-MAPK pathway in adults. So far, single cases of HCM treatment in patients with RASopathies have been described, with rapid improvement in both laboratory and echocardiographic parameters and regression of myocardial hypertrophy. Due to the described effectiveness, it is reasonable to verify these effects in a well-designed randomized study on a large group of patients.

Objective To evaluate the effectiveness of trametinib treatment in patients with HCM and a genetic mutation in the RAS/MAPK pathway.

Methodology

Randomized, open-label study. The study will include patients aged 0 to 18 with:

* mutation in the RAS/MAPK pathway confirmed by genetic tests
* HCM diagnosed by echocardiography

In the first phase of the study (3 months), patients will be randomly assigned to one of two groups:

* the intervention group will receive trametinib and standard treatment (beta-blocker and disopyramide)
* the control group will receive only standard treatment. Once this phase is complete, patients will be assessed. If higher effectiveness is demonstrated in the intervention group, in the second phase of the study, patients in the intervention group will continue their current treatment and patients in the control group will receive trametinib treatment. Each group will receive trametinib for 12 months.

Importance of the study The study results will provide grounds for routine introduction of MEK kinase inhibitors for the treatment of patients with HCM due to RASopathy. If effectiveness is demonstrated, this group will gain a simple, non-invasive and causal treatment option.

Conditions

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Cardiomegaly Noonan Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized control trial

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Trametynib

Trametynib in 0,025mg/kg dose orally once daily

Group Type EXPERIMENTAL

Trametinib tablet

Intervention Type DRUG

Trametynib orally once daily in 0,025mg/kg dose

Standard therapy

Disopiramide and Beta-blocker orally

Group Type ACTIVE_COMPARATOR

Standard therapy

Intervention Type DRUG

Disopiramide and Beta blockers orally

Interventions

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Trametinib tablet

Trametynib orally once daily in 0,025mg/kg dose

Intervention Type DRUG

Standard therapy

Disopiramide and Beta blockers orally

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* patient with diagnosed RASopathy
* patient with diagnosed hypertrophic cardiomyopathy
* signed innform consent

Exclusion Criteria

* contraindications to treatment with propranolol (drug hypersensitivity, atrioventricular block, severe bradycardia) disopyramide (drug hypersensitivity, WPW syndrome, atrioventricular block, QT prolongation) trametinib (drug hypersensitivity)
* lack of consent of the child's guardians to participate in the study

Minimum Eligible Age

1 Day

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No