The ReST Study
Research type
Research Study
Full title
A Study to Evaluate the Feasibility of Screening Relatives of Patients Affected by Non-Syndromic Thoracic Aortic Diseases: the ReST Study
IRAS ID
247434
Contact name
Gavin J. Murphy
Contact email
Sponsor organisation
University of Leicester
Clinicaltrials.gov Identifier
n/a, n/a
Duration of Study in the UK
1 years, 6 months, 1 days
Research summary
Research Summary
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, we 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 us to identify and treat this condition at the right time.
We therefore 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.Summary of Results
Diseases of the thoracic aorta (TADs) are increasing in prevalence. They commonly have a genetic cause and are characterised clinically by a long period without symptoms, followed by presentation as acute aortic syndromes when they have a mortality of up to 80%. Early diagnosis and treatment are therefore crucial elements for improving survival. Unlike syndromic TADs, non-syndromic (NS-TADs) forms are not evident from external physical features and abnormalities of other organs. This prevents early clinical detection and screening of the relatives of patients affected by NS-TAD using genetic and imaging tests (echocardiography, magnetic resonance imaging) and is recommended by current guidelines. However, the precise indications for genetic analysis or imaging are not well defined and screening in NS-TAD is not routine.Our group tackled this research need with ReST, a feasibility study that has been recently completed. In this project, several important aspects of the current pathway were highlighted. First, the diagnosis rate might be significantly high to warrant the need for screening even in patients and families that are currently not considered in the testing criteria. Secondly, the different modalities of screening might benefit from being integrated into a combined approach. Primary objective was to establish the requirements for a screening program in non-syndromic aortopathy. ReST showed how a combined approach to screening by means of an imaging test (ideally a combination of tests) and a genetic test is feasible and acceptable to patients. Nonetheless, our study also aimed at establishing referral and response rates among the 16 probands (index patients) and their first- and second-degree relatives. The reduced uptake of the testing offer from probands (and in a minor degree, from relatives) deserves attention in a larger, prospectively recruited cohort. We had planned to evaluate number/rate of relatives who would not undergo screening at the authors’ institution, because of their residence in different geographic regions or their wish to be exclude from the study. Our data do not allow us to clearly assess this issue. Participants reached our Centre from the Lincoln, Bristol and London area too, but a formal assessment of the reason behind the decline of the invitation to take part in the study cannot be performed without contacting screened individuals that have not consented to be contacted.
Although the sample size is limited, we obtained descriptive statistics for the diagnosis rate of the imaging modalities and of the genetic test, as planned in the design phase and in the study protocol. We also evaluated the perceptions of probands and family members in term of appropriateness of the screening and consent process, and determined the psychological impact related to the screening process for the probands and their relatives. We also could not identify any significant impact in terms of depression, anxiety and self-reported quality of life at the three months follow up. Lastly, although we could not evaluate the additional healthcare resource use attributable to the screening protocol with a formal health economics analysis, we were able to gain useful insights in terms of the expenses that would be needed to run this experience on a much larger scale. Overall, the funding allocated to the study was adequate and in line with the expenses foreseen during the design phase.REC name
East Midlands - Derby Research Ethics Committee
REC reference
18/EM/0287
Date of REC Opinion
3 Dec 2018
REC opinion
Further Information Favourable Opinion