Pathogenetic Basis of Aortopathy and Aortic Valve Disease

NCT03440697 | Active Not Recruiting

• 2 other identifiers: 20000414291509977311
• Study Type: observational
• Target: 3,000
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Aortopathies; Thoracic Aortic Aneurysm; Aortic Valve Disease; Thoracic Aortic Disease; Thoracic Aortic Dissection; Thoracic Aortic Rupture; Ascending Aortic Disease; Descending Aortic Disease; Ascending Aortic Aneurysm; Descending Aortic Aneurysm; Marfan Syndrome; Loeys-Dietz Syndrome; Vascular Ehlers-Danlos Syndrome; Shprintzen-Goldberg Syndrome; Turner Syndrome; PHACE Syndrome; Autosomal Recessive Cutis Laxa; Congenital Contractural Arachnodactyly; Arterial Tortuosity Syndrome; Bicuspid Aortic Valve-Associated Aortopathy; Bicuspid Aortic Valve; Familial Thoracic Aortic Aneurysm and Aortic Dissection

Keywords

Cardiac Disease; Cardiovascular Genetics

Outcome Measures

Primary Outcomes (2)

• Biorepository Establishment

  Establish a biorepository with detailed phenotype information to facilitate a broad spectrum of current and future studies

  20 years

• 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

Study Arms (6)

Aortopathy- 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)

Syndromic- Open to external enrollment

Subjects with a genetic diagnosis of Marfan Syndrome (MFS), Loeys-Dietz Syndrome (LDS), Vascular Ehlers-Danlos Syndrome (EDS) •positive genetic testing and/or a previous cardiac study required to be eligible

Aortopathy with Positive Genetic Results- Open to 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) who also have positive genetic testing results related to aortopathy.

Aortic Valve Disease- Closed to enrollment

Subjects with aortic valve disease (bicuspid, unicuspid, or tricuspid disease)

Family Members- Open to external enrollment

Family members of eligible subjects •Only family members of subjects with syndromic diagnoses are eligible for external enrollment at this time

Controls- Closed to external enrollment

Control subjects having tissue removed during a surgical procedure (e.g. coronary artery bypass graft surgery (CABG), cardiac transplant, etc.)

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

Families affected by aortopathy, aortic valve disease, or syndromic or genetic diagnosis that poses risk for the development of aortic disease who have not yet developed disease.

You may qualify if:

• 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.)

You may not qualify if:

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

Sponsors & Collaborators

• Yale University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (2)

Childrens Healthcare of Atlanta

Atlanta, Georgia, 30329, United States

Location

IU School of Medicine

Indianapolis, Indiana, 46202, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole Blood, Tissue, Saliva

MeSH Terms

Conditions

Aortic Aneurysm, Thoracic; Aortic Valve Disease; Dissection, Thoracic Aorta; Aneurysm, Ascending Aorta; Marfan Syndrome; Loeys-Dietz Syndrome; Ehlers-Danlos Syndrome, Type IV; Shprintzen Golberg craniosynostosis; Turner Syndrome; Aortic Aneurysm, Giant Congenital; Cutis Laxa, Autosomal Recessive, Type I; Congenital contractural arachnodactyly; Arterial Tortuosity Syndrome; Bicuspid Aortic Valve Disease; Aortic Aneurysm, Familial Thoracic 1; Heart Diseases

Condition Hierarchy (Ancestors)

Aortic Aneurysm; Aneurysm; Vascular Diseases; Cardiovascular Diseases; Aortic Diseases; Heart Valve Diseases; Aortic Dissection; Dissection, Blood Vessel; Acute Aortic Syndrome; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Ehlers-Danlos Syndrome; Hemostatic Disorders; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Abnormalities; Skin Diseases, Genetic; Collagen Diseases; Skin Diseases; Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Sex Chromosome Disorders of Sex Development; Male Urogenital Diseases; Sex Chromosome Disorders; Chromosome Disorders; Gonadal Disorders; Endocrine System Diseases

Study Officials

• Benjamin Landis, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2017
• First Posted: February 22, 2018
• Study Start: December 10, 2015
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)