An interventional study of WES and MRI in Screening, Aortic Aneurysm and Dissection and Genetic Disease, sponsored by University of Leicester. Status unknown at 1 site in United Kingdom. Open to participants aged 16 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-05-03.
Sponsored by University of Leicester · Not applicable, Interventional, and Prevention
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.
663 studies on the registry are indexed under Aortic Aneurysm; 117 are open to participants now.
This study's enrollment of 70 is above the median of 62 across 318 interventional studies indexed under Aortic Aneurysm.
Browse Aortic Aneurysm studies →University of Leicester is the lead sponsor of 166 studies on the registry; 51 are open to participants now.
Counted across the registry records on this site, refreshed daily.
FDR and SDR, aged 16 and above:
Exclusion Criteria:
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.
Genetic: WES · Diagnostic Test: MRI · Diagnostic Test: TTE · Other: Questionnaire
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.
Also known as: Whole exome sequencing
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.
Also known as: Magnetic resonance imaging
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.
Also known as: Trans-thoracic echocardiography
Acceptability questionnaires will be submitted to assess a baseline score of depression/anxiety that will be compared with a follow up value at three months
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
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
Aortic Compliance
Measured as an MRI feature of affected and unaffected thoracic aortas.
Time frame: Imaging tests completion, an average of 6 months.
Aortic Distensibility
Measured as an MRI feature of affected and unaffected thoracic aortas.
Time frame: Imaging tests completion, an average of 6 months.
Rates of concomitant external and cardiovascular characteristics
Rates of concomitant cardiovascular diseases (e.g. patent ductus arteriosus, cerebrovascular aneurysm) and external physical features (e.g. pectus excavates, livedo reticularis).
Time frame: Baseline clinical assessment
Response rate
Response rates (recruitment) among the probands and their relatives.
Time frame: Baseline clinical assessment
Acceptability questionnaires
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.
Time frame: Baseline and 3 months follow up
Depression evaluation
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.
Time frame: Baseline and 3 months follow up
Anxiety evaluation
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.
Time frame: Baseline and 3 months follow up
Health-related Quality of Life evaluation
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.
Time frame: Baseline and 3 months follow up
Resource use of genetic screening
Resource uses in terms of unitary costs of the genetic screening process.
Time frame: 3 months follow up
Resource use of imaging screening
Resource uses in terms of unitary costs of the imaging screening process.
Time frame: 3 months follow up
Resource use (hospital visits)
Number of participants reaching the research centre.
Time frame: 3 months follow up
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University of Leicester