Retrospective Natural History Study of RASopathy-associated Cardiomyopathy (RAS-CM)

NCT07344480 | Recruiting

• 1 other identifier: RAS-CM
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

RASopathy-associated hypertrophic cardiomyopathy (RAS-CM) is a disease with high morbidity and high mortality if presenting during infancy. Targeted therapies have shown significant activity in preclinical models and case reports. Drugs that target the underlying cause of this disease are now developed in cancer patients. Conducting randomized trials is not possible in severely ill infants with RAS-CM. Existing historical controls from older eras are not sufficient as external controls to support drug development as they lack critical clinical and genetic information to allow comparison with the cohort planned for future clinical trials. The purpose of this investigator-initiated retrospective natural history study is to collect clinical information and genetic information in patients with RAS-CM. The first goal is to establish a data set that meets regulatory requirements for the use as external control data in a future clinical trial, composing non-randomized, single-arm, open-label study cohorts. The second goal is to obtain natural history information that supports the selection of secondary exploratory endpoints chosen in a clinical trial.

Conditions

Heart Failure; RASopathy; Hypertrophic Cardiomyopathy (HCM)

Outcome Measures

Primary Outcomes (1)

• To define the one-year transplant-free survival rate of patients with infantile-onset RASopathy-associated hypertrophic cardiomyopathy, admitted to the hospital with congestive heart failure by 6 months of age.

  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**

Interventions

Retrospective data collection OTHER

Retrospective data collection, observation group are patients with genetic diagnosis of congenital RASopathy with hypertrophic cardiomyopathy and heart failure

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Deutsches Herzzentrum Muenchen: lead

Study Sites (1)

TUM Klinikum Deutsches Herzzentrum München

München, 80636, Germany

RECRUITING

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic; Heart Failure

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Central Study Contacts

Cordula Prof. Wolf

CONTACT

+49 89 1218-2441; wolf@dhm.mhn.de

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2026
• First Posted: January 15, 2026
• Study Start: June 17, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 18, 2026

Record last verified: 2025-10

Locations

DE (1)