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

NCT03861741 | Unknown DMC

• 1 other identifier: 0676
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Screening; Aortic Aneurysm and Dissection; Genetic Disease

Keywords

screening, aortic disease, mortality, genetic testing, imaging

Outcome Measures

Primary Outcomes (2)

• Rate of genetic diagnosis

  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

  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 Outcomes (16)

• Genetic variants

  Through study completion, an average of 1 year

• Family rate of genetic carriers

  Through study completion, an average of 1 year

• Penetrance

  Through study completion, an average of 1 year

• Mode of inheritance

  Through study completion, an average of 1 year

• Male: female preponderance

  Through study completion, an average of 1 year

Study Arms (1)

Participants

EXPERIMENTAL

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

Interventions

WES GENETIC

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

Participants

MRI DIAGNOSTIC_TEST

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

Participants

TTE DIAGNOSTIC_TEST

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

Participants

Questionnaire OTHER

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

Participants

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Leicester: lead

Study Sites (1)

Department of Cardiovascular Sciences

Leicester, Leicestershire, LE3 9QP, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 30371227 BACKGROUND

• 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.

  PMID: 35383466 DERIVED

MeSH Terms

Conditions

Aortic Dissection; Genetic Diseases, Inborn; Aortic Diseases

Interventions

Exome Sequencing; Magnetic Resonance Imaging; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Dissection, Blood Vessel; Aneurysm; Vascular Diseases; Cardiovascular Diseases; Acute Aortic Syndrome; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Whole Genome Sequencing; Sequence Analysis, DNA; Sequence Analysis; Genetic Techniques; Investigative Techniques; Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Gavin J Murphy, Prof

  University of Leicester

  PRINCIPAL INVESTIGATOR

• Giovanni Mariscalco, Prof

  University of Leicester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 18, 2019
• First Posted: March 4, 2019
• Study Start: March 1, 2019
• Primary Completion: May 20, 2022
• Study Completion: May 20, 2022
• Last Updated: May 3, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)