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

Not Applicable

• Conditions: Aortic Aneurysm and Dissection; Screening; Genetic Disease

• Registration Number: NCT03861741
• Lead Sponsor: University of Leicester

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2019-02-18
• Study First Submitted QC: 2019-02-28
• Study Start: 2019-03-01
• Study First Posted: 2019-03-04
• Status Verified: 2021-04
• Last Update Submitted: 2021-04-29
• Last Update Posted: 2021-05-03
• Primary Completion: 2022-05-20
• Study Completion: 2022-05-20

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 70

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Rate of genetic diagnosis	Through study completion, an average of 1 year	Frequency of first and second degree relatives with newly identified genetic loci associated with NS-TADs.
Rate of diagnosis through imaging modalities	At the end of recruitment stage, an average of 6 months	Frequency of newly diagnosed TAD through imaging modalities in first- and second-degree relatives of probands affected by NS-TADs.

Secondary Outcome Measures

Name	Time	Method
Penetrance	Through study completion, an average of 1 year	Genetic penetrance of the NS-TADs (proportion of individuals carrying a particular variant of a gene that are also affected by NS-TAD).
Mode of inheritance	Through study completion, an average of 1 year	Pattern of inheritance of the NS-TADs.
Aortic Distensibility	Imaging tests completion, an average of 6 months.	Measured as an MRI feature of affected and unaffected thoracic aortas.
Rates of concomitant external and cardiovascular characteristics	Baseline clinical assessment	Rates of concomitant cardiovascular diseases (e.g. patent ductus arteriosus, cerebrovascular aneurysm) and external physical features (e.g. pectus excavates, livedo reticularis).
Male: female preponderance	Through study completion, an average of 1 year	Male: female preponderance of NS-TADs.
Health-related Quality of Life evaluation	Baseline and 3 months follow up	Semi-quantitative evaluation of the impact of the screening process on health-related quality of life in probands and their relatives (baseline and 3 months), based on Short Form (36) Health Survey (SF-36) score. Said questionnaire is made up of eight scales, which are the weighted sums of the items for each section; a score of zero corresponds to maximum disability while 100 correlates to no disability.
Resource use (hospital visits)	3 months follow up	Number of participants reaching the research centre.
Genetic variants	Through study completion, an average of 1 year	Genetic variants associated with NS-TADs, identified from a panel of 55 loci, and rate of identification of each mutation.
Family rate of genetic carriers	Through study completion, an average of 1 year	Rate of genetic carriers in each affected family.
Aortic Compliance	Imaging tests completion, an average of 6 months.	Measured as an MRI feature of affected and unaffected thoracic aortas.
Response rate	Baseline clinical assessment	Response rates (recruitment) among the probands and their relatives.
Acceptability questionnaires	Baseline and 3 months follow up	Semi-quantitative evaluation of the participant experience awareness and acceptability of the screening and consent process, obtained by questionnaires administered to the patients and relatives.; Scales will be composed by 10 items, each can be rated with a score from 1 to 5. No threshold will be preset. Descriptive statistics will be used to present the results.
Depression evaluation	Baseline and 3 months follow up	Semi-quantitative evaluation of the impact of the screening process on depression in probands and their relatives (baseline and 3 months), based on Patient Health Questionnaire (PHQ-9) score. Score range goes from 0 to 27, proposed cut-off for active treatment is 15.
Anxiety evaluation	Baseline and 3 months follow up	Semi-quantitative evaluation of the impact of the screening process on anxiety in probands and their relatives (baseline and 3 months), based on Generalized Anxiety Disorder (GAD-7) score. Score range goes from 0 to 21, proposed cut-off for further assessment is 10.
Resource use of genetic screening	3 months follow up	Resource uses in terms of unitary costs of the genetic screening process.
Resource use of imaging screening	3 months follow up	Resource uses in terms of unitary costs of the imaging screening process.

Trial Locations

Locations (1)

Department of Cardiovascular Sciences; 🇬🇧 Leicester, Leicestershire, United Kingdom