Pathogenetic Basis of Aortopathy and Aortic Valve Disease

Aortic Valve Disease Clinical Trial

— TAA  

Official title:

Pathogenetic Basis of Aortopathy and Aortic Valve Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03440697
• Other study ID #: 1509977311
• Status: Recruiting
• Start date: December 10, 2015
• Est. completion date: December 31, 2030

Study information

• Verified date: March 2024
• Source: Indiana University
• Contact: Lindsey Helvaty, BS, BA
• Phone: 317-278-3020
• Email: lhelvaty[@]iu.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The main purpose of this study is to define the complex genetic and pathogenic basis of thoracic aortic aneurysm (TAA) and other forms of aortopathy and/or aortic valve disease by identifying novel disease-causing genes and by identifying important genetic modifiers for aortic and aortic valve disease severity.

Description:

Thoracic aortic aneurysm (TAA) is a type of aortopathy describing dilation of the proximal aortic dimensions including the aortic root, which is a risk factor for aortic dissection and sudden cardiac death. TAA and other forms of aortopathy (e.g. aortic tortuosity or aortic hypoplasia/stenosis) develop in the presence or absence of additional cardiovascular malformations including bicuspid aortic valve. TAA is associated with connective tissue disorders (e.g. Marfan syndrome), and familial clustering has been identified in a significant proportion of nonsyndromic cases, establishing high heritability. Pedigree analysis of TAA kindreds clearly identifies complex inheritance; however, progress towards understanding the genetic basis of TAA and other forms of aortopathy and, ultimately, the susceptibility to aortic dissection remains incomplete. There is a clinical need to develop novel methods for predicting disease risk based on genotype and phenotype, to further elucidate the genetic and pathogenic mechanisms of aortopathy, and to improve medical and surgical therapies. The overarching hypothesis of this study is that individual genetic variation modulates susceptibility to disease severity and progression. The goals of this study are 1) to ascertain a cohort of subjects who have aortopathy and/or aortic valve disease including TAA or who have genetic risk for the development of aortopathy and/or aortic valve disease, 2) to collect paired blood and tissue samples from well-characterized subjects, family members of subjects, and controls to perform genome-wide DNA sequence, histopathologic, transcriptional, and proteomic analyses, and 3) to establish a tissue biorepository with detailed phenotype information to facilitate a broad spectrum of current and future studies.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3000
• Est. completion date: December 31, 2030
• Est. primary completion date: December 31, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Open to external enrollment:
• Subjects with a genetic diagnosis of Marfan Syndrome (MDS), Loeys-Dietz Syndrome (LDS), or Vascular Ehlers-Danlos Syndrome (EDS); (Positive genetic testing or a previous cardiac study required to be eligible)
• Family members of eligible subjects (Only family members of subjects with syndromic diagnoses are eligible for external enrollment at this time)
• Closed to external enrollment:
• Subjects with aortic disease including TAA* or dissection, aortic tortuosity, or aortic hypoplasia/stenosis (based on any cardiac imaging modality including echocardiography, CT, MRI, or angiography)
• Subjects with aortic valve disease (bicuspid, unicuspid, or tricuspid disease)
• Control subjects having tissue removed during a surgical procedure (e.g. coronary artery bypass graft surgery (CABG), cardiac transplant, etc.)

Exclusion Criteria:

• Inability or unwillingness to provide consent (assent when indicated)

Related Conditions & MeSH terms

• Aneurysm
• Aortic Aneurysm
• Aortic Aneurysm, Thoracic
• Aortic Diseases
• Aortic Dissection
• Aortic Rupture
• Aortic Valve Disease
• Aortopathies
• Arterial Tortuosity Syndrome
• Ascending Aortic Aneurysm
• Ascending Aortic Disease
• Autosomal Recessive Cutis Laxa
• Bicuspid Aortic Valve
• Bicuspid Aortic Valve Disease
• Congenital Contractural Arachnodactyly
• Cutis Laxa
• Descending Aortic Aneurysm
• Descending Aortic Disease
• Ehlers-Danlos Syndrome
• Heart Defects, Congenital
• Heart Valve Diseases
• Loeys-Dietz Syndrome
• Marfan Syndrome
• PHACE Syndrome
• Rupture
• Shprintzen-Goldberg Syndrome
• Syndrome
• Thoracic Aortic Aneurysm
• Thoracic Aortic Disease
• Thoracic Aortic Dissection
• Thoracic Aortic Rupture
• Turner Syndrome
• Vascular Ehlers-Danlos Syndrome

Locations

Country	Name	City	State
United States	Childrens Healthcare of Atlanta	Atlanta	Georgia
United States	IU School of Medicine	Indianapolis	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Indiana University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biorepository Establishment	Establish a biorepository with detailed phenotype information to facilitate a broad spectrum of current and future studies	20 years
Primary	Genetic Analysis	The mechanisms of TAA pathogenesis will be determined by studying explanted aortic tissue and cells derived from patients with TAA for gene expression, protein expression, and other functional assays.	20 years