Clinical trial NCT04005976: Montalcino Aortic Consortium: Precision Medicine for Heritable Thoracic Aortic Disease
Official title: Montalcino Aortic Consortium: Precision Medicine for Heritable Thoracic Aortic Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Aortic Aneurysm
Aortic Dissection
Aortic Diseases
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
First posted: 2019-07-02
Enrollment: 5000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals with a known mutation for H-TAD and their relatives who also carry the mutation

Brief summary: The Montalcino Aortic Consortium (MAC) will provide the infrastructure to assemble large cohorts of patients with mutations in known heritable thoracic aortic disease (H-TAD) genes, define the phenotype associated with these genes, and determine genetic and environmental modifiers of H-TAD.

Detailed description: The MAC will provide the infrastructure to assemble large cohorts of patients with mutations in known H-TAD genes, define the phenotype associated with these genes, and determine genetic and environmental modifiers and other biomarkers of H-TAD. Recruitment of large numbers of patients world-wide will improve the precision of data used to predict disease risks. Retrospective and prospective study designs will be used to fully characterize the different stages of H-TAD (i.e. susceptibility, presymptomatic, and symptomatic) and other complications associated with the H-TAD genes, and examine clinical and environmental factors that define risk of aortic dissections. The data from MAC will provide the critical clinical information for precise management of thoracic aortic disease and other complications caused by mutations of these genes and improve the medical management and outcome of patients with genetically triggered, lethal vascular diseases.

Eligibility criteria: Inclusion Criteria:

* Patients and their relatives with a confirmed pathogenic, likely pathogenic variant, or variant of unknown clinical significance in at least one of the H-TAD genes (i.e. TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3, ACTA2, MYH11, MYLK, PRKG1, MAT2A, MFAP5, LOX, COL3A1, FOXE3, and FBN1).
* Patients of all ages, sex and race for which informed consent can be obtained.

Exclusion Criteria:

* Patients without a confirmed causative variant for H-TAD.

Primary outcomes:
measure: Number of participants with aortic dissection
timeFrame: 20 years
measure: Number of participants with aortic aneurysm requiring repair
timeFrame: 20 years
measure: Number of participants who died due to an aortic dissection/rupture or postoperative complications
timeFrame: 20 years
measure: Number of participants with aortic dilation
timeFrame: 20 years
measure: Rate of aortic growth
timeFrame: 20 years
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: The University of Texas Health Science Center at Houston
state: Texas
Study officials:
affiliation: UTHealth
name: Dianna Milewicz, MD, PhD
role: STUDY_DIRECTOR
References: