Clinical trial NCT03861741: A Study to Evaluate the Feasibility of Screening Relatives of Patients Affected by Non-Syndromic Thoracic Aortic Diseases
Official title: A Study to Evaluate the Feasibility of Screening Relatives of Patients Affected by Non-Syndromic Thoracic Aortic Diseases: The ReST Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Screening
Aortic Aneurysm and Dissection
Genetic Disease
Keywords: screening, aortic disease, mortality, genetic testing, imaging
Lead sponsor: University of Leicester
Sponsor class: OTHER
First posted: 2019-03-04
Enrollment: 70
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This pilot study will recruit relatives of 16 patients with a diagnosis of non-syndromic thoracic aortic disease. As many FDR and SDR of the proband (index patient) as possible will be recruited into the study (family based analysis). They will be screened through complete clinical evaluations, genetic tests (whole exome sequencing) and imaging modalities (TTE and MRI) for the presence of newly NS-TADs.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of genetic diagnosis
timeFrame: Through study completion, an average of 1 year
measure: Rate of diagnosis through imaging modalities
timeFrame: At the end of recruitment stage, an average of 6 months
Secondary outcomes:
measure: Genetic variants
timeFrame: Through study completion, an average of 1 year
measure: Family rate of genetic carriers
timeFrame: Through study completion, an average of 1 year
measure: Penetrance
timeFrame: Through study completion, an average of 1 year
measure: Mode of inheritance
timeFrame: Through study completion, an average of 1 year
measure: Male: female preponderance
timeFrame: Through study completion, an average of 1 year
measure: Aortic Compliance
timeFrame: Imaging tests completion, an average of 6 months.
measure: Aortic Distensibility
timeFrame: Imaging tests completion, an average of 6 months.
measure: Rates of concomitant external and cardiovascular characteristics
timeFrame: Baseline clinical assessment
measure: Response rate
timeFrame: Baseline clinical assessment
measure: Acceptability questionnaires
timeFrame: Baseline and 3 months follow up
measure: Depression evaluation
timeFrame: Baseline and 3 months follow up
measure: Anxiety evaluation
timeFrame: Baseline and 3 months follow up
measure: Health-related Quality of Life evaluation
timeFrame: Baseline and 3 months follow up
measure: Resource use of genetic screening
timeFrame: 3 months follow up
measure: Resource use of imaging screening
timeFrame: 3 months follow up
measure: Resource use (hospital visits)
timeFrame: 3 months follow up
Other outcomes:
Locations:
city: Leicester
country: United Kingdom
facility: Department of Cardiovascular Sciences
state: Leicestershire
Study officials:
affiliation: University of Leicester
name: Gavin J Murphy, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Leicester
name: Giovanni Mariscalco, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mariscalco G, Debiec R, Elefteriades JA, Samani NJ, Murphy GJ. Systematic Review of Studies That Have Evaluated Screening Tests in Relatives of Patients Affected by Nonsyndromic Thoracic Aortic Disease. J Am Heart Assoc. 2018 Aug 7;7(15):e009302. doi: 10.1161/JAHA.118.009302.
citation: Abbasciano RG, Mariscalco G, Barwell J, Owens G, Zakkar M, Joel-David L, Pathak S, Adebayo A, Shannon N, Haines RL, Aujla H, Eagle-Hemming B, Kumar T, Lai F, Wozniak M, Murphy G. Evaluating the Feasibility of Screening Relatives of Patients Affected by Nonsyndromic Thoracic Aortic Diseases: The REST Study. J Am Heart Assoc. 2022 Apr 19;11(8):e023741. doi: 10.1161/JAHA.121.023741. Epub 2022 Apr 6.