A Study to Evaluate the Feasibility of Screening Relatives of Patients Affected by Non-Syndromic Thoracic Aortic Diseases
- Conditions
- Aortic Aneurysm and DissectionScreeningGenetic Disease
- Interventions
- Genetic: WESDiagnostic Test: MRIDiagnostic Test: TTEOther: Questionnaire
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 70
-
NS-TAD probands operated on (n=16).
-
FDR and SDR, aged 16 and above:
- At least two relatives willing to participate in the screening programme.
- Relatives able to understand English.
- 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.
- Probands with aortic lesions associated with trauma and infections.
- Probands/relatives unable to give informed consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Participants Questionnaire All participants will be screened through complete clinical evaluations, genetic tests and imaging modalities (TTE and MRI) for the presence of newly Non Syndromic-Thoracic Aortic Diseases. Demographic and clinical data from all participants will be collected using case report forms, and by accessing their medical records. Data on imaging investigations will be obtained from TTE and MRI. Blood samples will be used for the purpose of isolation of genetic material and subsequent whole exome sequencing along with the analysis of selected loci. Additional citrated blood samples and plasma will be collected and stored for the potential analysis of circulating microvesicles and miRNA. Participants WES All participants will be screened through complete clinical evaluations, genetic tests and imaging modalities (TTE and MRI) for the presence of newly Non Syndromic-Thoracic Aortic Diseases. Demographic and clinical data from all participants will be collected using case report forms, and by accessing their medical records. Data on imaging investigations will be obtained from TTE and MRI. Blood samples will be used for the purpose of isolation of genetic material and subsequent whole exome sequencing along with the analysis of selected loci. Additional citrated blood samples and plasma will be collected and stored for the potential analysis of circulating microvesicles and miRNA. Participants MRI All participants will be screened through complete clinical evaluations, genetic tests and imaging modalities (TTE and MRI) for the presence of newly Non Syndromic-Thoracic Aortic Diseases. Demographic and clinical data from all participants will be collected using case report forms, and by accessing their medical records. Data on imaging investigations will be obtained from TTE and MRI. Blood samples will be used for the purpose of isolation of genetic material and subsequent whole exome sequencing along with the analysis of selected loci. Additional citrated blood samples and plasma will be collected and stored for the potential analysis of circulating microvesicles and miRNA. Participants TTE All participants will be screened through complete clinical evaluations, genetic tests and imaging modalities (TTE and MRI) for the presence of newly Non Syndromic-Thoracic Aortic Diseases. Demographic and clinical data from all participants will be collected using case report forms, and by accessing their medical records. Data on imaging investigations will be obtained from TTE and MRI. Blood samples will be used for the purpose of isolation of genetic material and subsequent whole exome sequencing along with the analysis of selected loci. Additional citrated blood samples and plasma will be collected and stored for the potential analysis of circulating microvesicles and miRNA.
- 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 Aortic Distensibility Imaging tests completion, an average of 6 months. Measured as an MRI feature of affected and unaffected thoracic aortas.
Male: female preponderance Through study completion, an average of 1 year Male: female preponderance of NS-TADs.
Response rate Baseline clinical assessment Response rates (recruitment) among the probands and their relatives.
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.
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).
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.
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