A Study to Evaluate the Feasibility of Screening Relatives of Patients Affected by Non-Syndromic Thoracic Aortic Diseases

University of Leicester70 enrolled

Overview

The primary hypothesis is that a tailored programme of genetic and imaging screening of first- and second-degree relatives of patients affected by non-syndromic forms of thoracic aortic diseases will identify individuals at risk of death from these conditions. These individuals would constitute specific population of patients, requiring dedicated imaging surveillance and/or earlier prophylactic aortic surgery.

Diseases involving the thoracic aorta (the major artery in the body) are a major health problem affecting an increasing number of people worldwide. In particular, a group of these conditions termed Non-Syndromic Aortic Diseases (NS-TAD), can develop without any obvious symptoms or external features which prevents early identification. Unfortunately, if not treated, the aorta may enlarge and lead to dissection, a life-threatening medical emergency. For this reason, the investigators believe it might be helpful to investigate relatives of patients undergoing surgery for thoracic aortic disease to understand if there are tests that could help identify and treat this condition at the right time. Therefore the investigators propose to conduct a feasibility study to identify the practical issues and challenges that would need to be overcome in order to perform a successful tailored genetic (by collecting a small blood sample) and imaging (with exams such as echocardiography and MRI) screening in such population of individuals. Moreover, all participants will receive two questionnaires to ask their opinion about the study and to measure their levels of anxiety and depression, to judge whether and how this study has affected their emotional status. The study will be carried out at the Department of Cardiovascular Sciences Glenfield Hospital, University Hospitals of Leicester NHS Trust.

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Screening Aortic Aneurysm and Dissection Genetic Disease

Interventions

WESGENETIC

A peripheral venous blood sample will be processed internally, and externally subjected to WES. Only genetic material from relatives of probands in which a mutation has been identified will be sequenced.

MRIDIAGNOSTIC_TEST

A MRI of the thoracic aorta will be performed in all relatives able to attend the Glenfield Hospital and who have no contra-indications to this imaging modality; pulse-wave velocity will be recorded.

TTEDIAGNOSTIC_TEST

TTE screening will be performed by a trained physiologist. Aortic diameter will be measured from the parasternal long-axis view at the sinuses of Valsalva and at the widest level of the ascending aorta. All measurements will be made in end-diastole.

Eligibility

Sex: ALLMin age: 16 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. NS-TAD probands operated on (n=16). 2. FDR and SDR, aged 16 and above: 1. At least two relatives willing to participate in the screening programme. 2. Relatives able to understand English. Exclusion Criteria: 1. Probands with syndromic aortopathies, including Marfan Syndrome, Loeys-Dietz Syndrome, Ehlers-Danlos Syndrome, Shprintzen-Goldberg syndrome, aneurysm-osteoarthritis syndrome, arterial tortuosity syndrome, and cutis laxa syndrome. 2. Probands with aortic lesions associated with trauma and infections. 3. Probands/relatives unable to give informed consent

Locations (1)

Department of Cardiovascular Sciences

Leicester, Leicestershire, United Kingdom

Outcomes

Primary Outcomes

Rate of genetic diagnosis

Frequency of first and second degree relatives with newly identified genetic loci associated with NS-TADs.

Time frame: Through study completion, an average of 1 year

Rate of diagnosis through imaging modalities

Frequency of newly diagnosed TAD through imaging modalities in first- and second-degree relatives of probands affected by NS-TADs.

Time frame: At the end of recruitment stage, an average of 6 months

Secondary Outcomes

Genetic variants

Genetic variants associated with NS-TADs, identified from a panel of 55 loci, and rate of identification of each mutation.

Time frame: Through study completion, an average of 1 year

Family rate of genetic carriers

Rate of genetic carriers in each affected family.

Time frame: Through study completion, an average of 1 year

Penetrance

Genetic penetrance of the NS-TADs (proportion of individuals carrying a particular variant of a gene that are also affected by NS-TAD).

Time frame: Through study completion, an average of 1 year

Mode of inheritance

Pattern of inheritance of the NS-TADs.

Time frame: Through study completion, an average of 1 year

Male: female preponderance

Male: female preponderance of NS-TADs.

Time frame: Through study completion, an average of 1 year

Data from ClinicalTrials.gov

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