The BRAVE Study- The Identification of Genetic Variants Associated With Bicuspid Aortic Valve Using a Combination of Case-control and Family-based Approaches.

NCT04514445 | Recruiting

• 1 other identifier: EDGE: 51674
• Study Type: observational
• Target: 700
• Locations: 1 country
• Sites: 4

Brief Summary

Bicuspid aortic valve (BAV) is the most common congenital heart anomaly in the general population (1-2% of all individuals). In affected people, the aortic valve (the structure ensuring one way blood flow between the heart's left pumping chamber, the left ventricle and the main body artery, the aorta) consists of 2 rather than 3 leaflets. This arrangement can cause the affected valve to have restricted opening or cause it to leak. Both situations put strain on the heart and patients with BAV across the age range may require surgery to replace the affected valve. BAV is therefore a condition associated with significant ill health and early mortality. BAV is known to cluster in families and is likely to have a genetic cause. We don't fully understand the inheritance of BAV or the specific genes involved in its development. Learning more about this is the basis of the BRAVE study. We will ask patients with BAV and their relatives (who may or may not have BAV) to take part in the study. Blood samples obtained from the participants will be used for analyses of their genetic composition. This information, linked with the clinical data concerning who does and does not have BAV, will potentially enable the identification of the gene changes responsible for the disease. This, we hope, will give us a much better understanding of the mechanisms leading to this serious and common condition.

Conditions

Cardiovascular Diseases

Outcome Measures

Primary Outcomes (1)

• The primary objective of the BRAVE study is to identify genetic loci associated with BAV.

  The main analyses will consist of identifying and cataloguing genetic variants for each individual from the DNA sequencing and then seeing whether any particular variant or sets of variants are more commonly present in BAV subjects versus those without BAV (case-control design) or present in subjects with BAV but not in unaffected family members (family-based approach).

  48 Months

Interventions

Observational OTHER

Eligibility Criteria

• Age: 10 Years - 99 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Suitable patients with the condition (index patients) will be identified and invited to take part in the study by their healthcare teams. Relatives will be identified during the interview with the index patient and invited to take part in the study by the index patients. Subjects below the age of 18 will be provided with age specific documents (information leaflets, invitation letters and consent forms). Informed consent will be sought from such participants as well as parent or legal guardian of such participants.

You may qualify if:

• \- 1. All outpatients and inpatients with diagnosed BAV, of either gender, aged 10 and above.
• \. Affected and unaffected first degree relatives meeting the age criteria.

You may not qualify if:

• \) Patients unable to give informed consent.
• \) Patients known to be infected with HIV, Hepatitis B, Hepatitis C or any other agent posing an infection risk from unfixed material.
• \) Patient with known cytogenetic disorders e.g. aneuploidia, chromosomal abnormalities and known karyotype abnormalities.
• \) Patients with diagnosed or suspected Mendelian syndromes (e.g. Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome).

Sponsors & Collaborators

• University Hospitals, Leicester: lead

Study Sites (4)

Kettering General Hospital

Kettering, United Kingdom

RECRUITING

University Hospitals of Leicester

Leicester, United Kingdom

RECRUITING

Imperial College Healthcare NHS Trust

London, United Kingdom

RECRUITING

Sheffield Teaching Hospital NHS Foundation Trust

Sheffield, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, serum and plasma to be retained at minus 80 degrees

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Watchful Waiting

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Study Officials

• Aidan Bolger, Dr

  Principal Investigator

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aidan Bolger, Dr

CONTACT

aidan.bolger@uhl-tr.nhs.uk

Radek Debiec, Dr

CONTACT

radoslaw.debiec@uhl-tr.nhs.uk

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2020
• First Posted: August 17, 2020
• Study Start: September 8, 2015
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (4)