Natural history of RASopathy-associated cardiomyopathy in infants and children
Retrospective Natural History Study of RASopathy-associated Cardiomyopathy (RAS-CM)
This project collects clinical and genetic records from infants and children with genetically confirmed RASopathy-associated hypertrophic cardiomyopathy to create a comparison dataset for future treatments.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 100 (estimated) |
| Sex | All |
| Sponsor | Deutsches Herzzentrum Muenchen Academic / other |
| Locations | 1 site (München) |
| Trial ID | NCT07344480 on ClinicalTrials.gov |
What this trial studies
This retrospective effort gathers clinical, imaging, and genetic data from patients with molecularly confirmed RASopathies who developed myocardial hypertrophy and were hospitalized between 01/01/2015 and 06/30/2019. Eligible cases require a pathogenic or likely pathogenic variant in a RAS‑MAPK gene and echocardiographic evidence of hypertrophy (z-score > 2), including those with congestive heart failure or progression to heart failure within the first six months of life. Patients who received mTOR or MEK inhibitors are excluded. The goal is to build a well-characterized dataset that meets regulatory expectations to serve as external control data for single-arm trials of targeted therapies in severely ill infants with RAS-CM.
Who should consider this trial
Good fit: Ideal records are from infants or children with a confirmed pathogenic/likely pathogenic RASopathy variant, echocardiographic myocardial hypertrophy (z-score > 2), and hospital admission for or progression to congestive heart failure within the first six months of life (admitted between 01/01/2015 and 06/30/2019).
Not a fit: Patients who received mTOR or MEK inhibitors, do not have a confirmed pathogenic/likely pathogenic RASopathy variant, lack echocardiographic hypertrophy, or were not hospitalized in the specified time window are unlikely to be included or benefit from this dataset.
Why it matters
Potential benefit: If successful, this dataset could provide regulatory-grade external control data that helps speed development and approval of targeted treatments for infants with RAS-CM.
How similar studies have performed: Targeted therapies for RASopathy-associated cardiomyopathy have shown promise in preclinical models and case reports, but well-characterized retrospective external-control datasets for RAS-CM are limited.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Molecular genetic diagnosis of a RASopathy (i.e., a pathogenic or likely pathogenic variant in one of the RAS-MAPK pathway genes identified, irrespective of when performed) * Imaging diagnosis of myocardial hypertrophy (echocardiography) showing a maximal end-diastolic wall thickness of greater than normal (z-score \> 2) with or without outflow tract obstruction * Admitted to hospital between 01/01/2015 and 06/30/2019 for congestive heart failure\* or developing progressive congestive heart failure during any hospital stay within first 6 months of life\*\* * Ross score calculated from medical history and physical examination notes in the absence of any other reason prompting hospital admission (e.g., elective procedure, other organ dysfunction, etc.); \*\*: defined by Ross Score greater than 2 Exclusion Criteria: * Receiving mechanistic Target of Rapamycin Inhibitor (mTOR inhibitor) and/or Mitogen-Activated Protein Kinase Kinase Inhibitor (MEK inhibitors) * Inability to identify or retrospectively calculate the patient´s Ross Score within the first six months of life
Where this trial is running
München
- TUM Klinikum Deutsches Herzzentrum München — München, Germany (Recruiting)
Study contacts
- Study coordinator: Cordula Prof. Wolf
- Email: wolf@dhm.mhn.de
- Phone: +49 89 1218-2441
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.