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

April 29, 2021 updated by: University of Leicester

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

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.

Study Overview

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 Type

Interventional

Enrollment (Actual)

70

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Leicestershire
      • Leicester, Leicestershire, United Kingdom, LE3 9QP
        • Department of Cardiovascular Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Participants
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.
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.
Other Names:
  • 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.
Other Names:
  • 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.
Other Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of genetic diagnosis
Time Frame: Through study completion, an average of 1 year
Frequency of first and second degree relatives with newly identified genetic loci associated with NS-TADs.
Through study completion, an average of 1 year
Rate of diagnosis through imaging modalities
Time Frame: 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.
At the end of recruitment stage, an average of 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genetic variants
Time Frame: 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.
Through study completion, an average of 1 year
Family rate of genetic carriers
Time Frame: Through study completion, an average of 1 year
Rate of genetic carriers in each affected family.
Through study completion, an average of 1 year
Penetrance
Time Frame: 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).
Through study completion, an average of 1 year
Mode of inheritance
Time Frame: Through study completion, an average of 1 year
Pattern of inheritance of the NS-TADs.
Through study completion, an average of 1 year
Male: female preponderance
Time Frame: Through study completion, an average of 1 year
Male: female preponderance of NS-TADs.
Through study completion, an average of 1 year
Aortic Compliance
Time Frame: Imaging tests completion, an average of 6 months.
Measured as an MRI feature of affected and unaffected thoracic aortas.
Imaging tests completion, an average of 6 months.
Aortic Distensibility
Time Frame: Imaging tests completion, an average of 6 months.
Measured as an MRI feature of affected and unaffected thoracic aortas.
Imaging tests completion, an average of 6 months.
Rates of concomitant external and cardiovascular characteristics
Time Frame: 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).
Baseline clinical assessment
Response rate
Time Frame: Baseline clinical assessment
Response rates (recruitment) among the probands and their relatives.
Baseline clinical assessment
Acceptability questionnaires
Time Frame: 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.

Baseline and 3 months follow up
Depression evaluation
Time Frame: 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.
Baseline and 3 months follow up
Anxiety evaluation
Time Frame: 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.
Baseline and 3 months follow up
Health-related Quality of Life evaluation
Time Frame: 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.
Baseline and 3 months follow up
Resource use of genetic screening
Time Frame: 3 months follow up
Resource uses in terms of unitary costs of the genetic screening process.
3 months follow up
Resource use of imaging screening
Time Frame: 3 months follow up
Resource uses in terms of unitary costs of the imaging screening process.
3 months follow up
Resource use (hospital visits)
Time Frame: 3 months follow up
Number of participants reaching the research centre.
3 months follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Giovanni Mariscalco, Prof, University of Leicester

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2019

Primary Completion (Anticipated)

May 20, 2022

Study Completion (Anticipated)

May 20, 2022

Study Registration Dates

First Submitted

February 18, 2019

First Submitted That Met QC Criteria

February 28, 2019

First Posted (Actual)

March 4, 2019

Study Record Updates

Last Update Posted (Actual)

May 3, 2021

Last Update Submitted That Met QC Criteria

April 29, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Genetic Disease

Clinical Trials on WES

3
Subscribe