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

Last updated: August 12, 2024
Sponsor: Medical University of Warsaw
Overall Status: Active - Recruiting

Phase

2

Condition

Hypogonadism

Severe Short Stature

Circulation Disorders

Treatment

Standard therapy

Trametinib tablet

Clinical Study ID

NCT06555237
KB/16/2024
  • Ages 1-18
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • patient with diagnosed RASopathy

  • patient with diagnosed hypertrophic cardiomyopathy

  • signed innform consent

Exclusion

Exclusion Criteria:

  • contraindications to treatment with propranolol (drug hypersensitivity,atrioventricular block, severe bradycardia) disopyramide (drug hypersensitivity, WPWsyndrome, atrioventricular block, QT prolongation) trametinib (drughypersensitivity)

  • lack of consent of the child's guardians to participate in the study

Study Design

Total Participants: 40
Treatment Group(s): 2
Primary Treatment: Standard therapy
Phase: 2
Study Start date:
August 01, 2024
Estimated Completion Date:
December 01, 2026

Study Description

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.

Connect with a study center

  • Department of Paediatrics, The Medical University of Warsaw, Poland

    Warsaw, 02-091
    Poland

    Active - Recruiting

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