New Diagnostic Strategy in Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy Clinical Trial

— HYPERGEN  

Official title:

New Diagnostic Strategy in Hypertrophic Cardiomyopathy Including a New Genetic Approach: A Multicentric Prospective Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02520856
• Other study ID #: 2014-29
• Secondary ID: RCAPHM14_0358
• Status: Recruiting
• Phase: N/A
• First received: August 5, 2015
• Last updated: August 7, 2015
• Start date: July 2015
• Est. completion date: July 2018

Study information

• Verified date: August 2015
• Source: Assistance Publique Hopitaux De Marseille
• Contact: Gilbert HABIB, Professor
• Email: gilbert.habib[@]ap-hm.fr
• Is FDA regulated: No
• Health authority: France: Comité consultatif sur le traitement de l'information en matière de recherche dans le domaine de la santéFrance: Commission nationale de l'informatique et des libertés
• Study type: Observational

Clinical Trial Summary

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease characterized by unexplained hypertrophy of the left ventricle, often with predominant involvement of the interventricular septum, and characterized by myocyte disarray and fibrosis.

HCM is the most common familial heart disease with strong genetic heterogeneity, demonstrated over the past 20 years. Mutations in 11 or more genes encoding proteins of the cardiac sarcomere are responsible for (or associated with) HCM.

However, 30-40% of sporadic and familial cases of HCM are still genetically unlabelled. In addition, secondary HCM caused by Fabry's disease or amyloidosis, may mimic primary HCM and may be under diagnosed. This may result in a delay in accurate diagnosis and instauration of specific treatment, with possible clinical consequences for the patients.

For these reasons, we decided to apply a new diagnostic strategy for patients with newly diagnosed HCM, including the whole exome sequencing (WES) technology.

If correctly applied, this new technology has the potential to strongly reduce the diagnostic wavering leading to earlier diagnosis and genetic counseling in sarcomeric HCM and rarer forms of secondary HCM including Fabry's disease and amyloidosis, and also specific therapy set-up in secondary forms of HCM. It should also allow identifying new genes responsible for HCM.

Description:

Background : Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease characterized by unexplained hypertrophy of the left ventricle, often with predominant involvement of the interventricular septum, and characterized by myocyte disarray and fibrosis.

HCM is the most common familial heart disease with strong genetic heterogeneity, demonstrated over the past 20 years. Mutations in 11 or more genes encoding proteins of the cardiac sarcomere are responsible for (or associated with) HCM.

However, 30-40% of sporadic and familial cases of HCM are still genetically unlabelled. In addition, secondary HCM caused by Fabry's disease or amyloidosis, may mimic primary HCM and may be under diagnosed. This may result in a delay in accurate diagnosis and instauration of specific treatment, with possible clinical consequences for the patients.

Objectives : For these reasons, we decided to apply a new diagnostic strategy for patients with newly diagnosed HCM, including the whole exome sequencing (WES) technology.

1. Main objective: to evaluate the additional diagnostic value of the new proposed strategy for the identification of a specific cause of HCM as compared with conventional diagnostic strategy

2. Secondary objectives:

To evaluate the frequency of secondary HCM (Fabry's disease, amyloidosis, mitochondrial cardiomyopathies, and others) observed by this systematic screening in a population of newly diagnosed HCM

Perspectives: If correctly applied, this new technology has the potential to strongly reduce the diagnostic wavering leading to earlier diagnosis and genetic counseling in sarcomeric HCM and rarer forms of secondary HCM including Fabry's disease and amyloidosis, and also specific therapy set-up in secondary forms of HCM. It should also allow identifying new genes responsible for HCM.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: July 2018
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• patient with newly diagnosed hypertrophic cardiomyopathy (HCM), based on conventional echocardiographic criteria.The diagnosis of HCM will be considered definite in the presence of left ventricle hypertrophy without cavity dilatation and without other cardiac or systemic disease able to produce the magnitude of hypertrophy.

Exclusion Criteria:

• Associated cardiac or non cardiac disease known to cause left ventricle hypertrophy (uncontrolled systemic Hypertension, severe aortic stenosis)

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Hypertrophic
• Hypertrophic Cardiomyopathy
• Hypertrophy

Intervention

Other:
• blood sample

Locations

Country	Name	City	State
France	Assistance Publique Hôpitaux de Marseille	Marseille

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique Hopitaux De Marseille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	whole exome sequencing		12 months	No
Primary	Classic genetic analysis		12 months	No