TAA: Pathogenetic Basis of Aortopathy and Aortic Valve Disease

Sponsor
Indiana University (Other)
Overall Status
Recruiting
CT.gov ID
NCT03440697
Collaborator
(none)
3,000
1
156
19.2

Study Details

Study Description

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.

Detailed 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.

Study Design

Study Type:
Observational
Anticipated Enrollment :
3000 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Pathogenetic Basis of Aortopathy and Aortic Valve Disease
Study Start Date :
Dec 1, 2015
Anticipated Primary Completion Date :
Dec 1, 2025
Anticipated Study Completion Date :
Dec 1, 2028

Arms and Interventions

Arm Intervention/Treatment
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.)

Outcome Measures

Primary Outcome Measures

  1. Biorepository Establishment [10 years]

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

  2. DNA Sequence Analysis [10 years]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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)

Contacts and Locations

Locations

Site City State Country Postal Code
1 IU School of Medicine Indianapolis Indiana United States 46202

Sponsors and Collaborators

  • Indiana University

Investigators

  • Principal Investigator: Benjamin Landis, MD, IU School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Benjamin Landis, Assistant Professor of Pediatrics and Medical and Molecular Genetics, Indiana University
ClinicalTrials.gov Identifier:
NCT03440697
Other Study ID Numbers:
  • 1509977311
First Posted:
Feb 22, 2018
Last Update Posted:
Jan 20, 2022
Last Verified:
Jan 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Benjamin Landis, Assistant Professor of Pediatrics and Medical and Molecular Genetics, Indiana University
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jan 20, 2022