ScreeningReSTNCT03861741
A Study to Evaluate the Feasibility of Screening Relatives of Patients Affected by Non-Syndromic Thoracic Aortic Diseases
A study testing WES, MRI and TTE in people with Screening and Aortic Aneurysm and Dissection, run by University of Leicester at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and olderHealthy volunteers can take part
- Conditions the study is for
- Screening, Aortic Aneurysm and Dissection, Genetic Disease
- What is being tested?
- WES, MRI and TTE
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Mar 2019to 20 May 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Department of Cardiovascular Sciences
Leicester, Leicestershire, LE3 9QP
About this study
Official title: 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.
Read the 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.
- Conditions
- Screening, Aortic Aneurysm and Dissection, Genetic Disease
- Being tested
- WES, MRI, TTE, Questionnaire
- Keywords
- screening, aortic disease, mortality, genetic testing, imaging
- Medical subject headings
- Aortic Dissection, Genetic Diseases, Inborn, Aortic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WESGenetic
Also called Whole exome sequencing
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.
MRIDiagnostic test
Also called Magnetic resonance imaging
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.
TTEDiagnostic test
Also called Trans-thoracic echocardiography
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.
QuestionnaireOther
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Genetic: WES; Diagnostic Test: MRI; Diagnostic Test: TTE; Other: Questionnaire |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of genetic diagnosis
Frequency of first and second degree relatives with newly identified genetic loci associated with NS-TADs.
Measured: 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.
Measured: At the end of recruitment stage, an average of 6 months
Secondary outcomes (16)
Genetic variants
Genetic variants associated with NS-TADs, identified from a panel of 55 loci, and rate of identification of each mutation.
Measured: Through study completion, an average of 1 year
Family rate of genetic carriers
Rate of genetic carriers in each affected family.
Measured: 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).
Measured: Through study completion, an average of 1 year
Mode of inheritance
Pattern of inheritance of the NS-TADs.
Measured: Through study completion, an average of 1 year
Male: female preponderance
Male: female preponderance of NS-TADs.
Measured: Through study completion, an average of 1 year
Aortic Compliance
Measured as an MRI feature of affected and unaffected thoracic aortas.
Measured: Imaging tests completion, an average of 6 months.
Aortic Distensibility
Measured as an MRI feature of affected and unaffected thoracic aortas.
Measured: 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).
Measured: Baseline clinical assessment
Response rate
Response rates (recruitment) among the probands and their relatives.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and 3 months follow up
Resource use of genetic screening
Resource uses in terms of unitary costs of the genetic screening process.
Measured: 3 months follow up
Resource use of imaging screening
Resource uses in terms of unitary costs of the imaging screening process.
Measured: 3 months follow up
Resource use (hospital visits)
Number of participants reaching the research centre.
Measured: 3 months follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2019
- Study start1 Mar 2019
- Primary completion20 May 2022 (estimated)
- Study completion20 May 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ScreeningStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- 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.
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leicester
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gavin J Murphy, Prof, Principal investigator, University of LeicesterGiovanni Mariscalco, Prof, Principal investigator, University of Leicester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03861741
- Sponsor's protocol ID
- 0676
- Acronym
- ReST
- Status last verified
- Apr 2021
- First submitted
- 18 Feb 2019
- Last updated
- 3 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 30371227Abbasciano 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.
PubMed 35383466
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Evaluate the Feasibility of Screening Relatives of Patients Affected by Non-Syndromic Thoracic Aortic Diseases: The ReST Study
- ClinicalTrials.gov ID
- NCT03861741
- Acronym / sponsor ID
- ReST / 0676
- Conditions
- Screening, Aortic Aneurysm and Dissection, Genetic Disease
- Keywords
- screening, aortic disease, mortality, genetic testing, imaging
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (actual)
- Lead sponsor
- University of LeicesterUniversity, hospital or other
- Study start
- 1 Mar 2019 (actual)
- Primary completion
- 20 May 2022 (estimated)
- Study completion
- 20 May 2022 (estimated)
- First posted
- 4 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Participants | Experimental | Genetic: WES, Diagnostic Test: MRI, Diagnostic Test: TTE, Other: QuestionnaireAll 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. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- NS-TAD probands operated on (n=16).
- FDR and SDR, aged 16 and above:
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| WESAlso: Whole exome sequencingA 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. | Genetic | Participants |
| MRIAlso: Magnetic resonance imagingA 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. | Diagnostic test | Participants |
| TTEAlso: Trans-thoracic echocardiographyTTE 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. | Diagnostic test | Participants |
| QuestionnaireAcceptability questionnaires will be submitted to assess a baseline score of depression/anxiety that will be compared with a follow up value at three months | Other | Participants |
Primary outcome
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.
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.
16 secondary outcomes
Genetic variants
Time frame: Through study completion, an average of 1 year
Family rate of genetic carriers
Time frame: Through study completion, an average of 1 year
Penetrance
Time frame: Through study completion, an average of 1 year
Mode of inheritance
Time frame: Through study completion, an average of 1 year
Male: female preponderance
Time frame: Through study completion, an average of 1 year
Aortic Compliance
Time frame: Imaging tests completion, an average of 6 months.
Aortic Distensibility
Time frame: Imaging tests completion, an average of 6 months.
Rates of concomitant external and cardiovascular characteristics
Time frame: Baseline clinical assessment
Response rate
Time frame: Baseline clinical assessment
Acceptability questionnaires
Time frame: Baseline and 3 months follow up
Depression evaluation
Time frame: Baseline and 3 months follow up
Anxiety evaluation
Time frame: Baseline and 3 months follow up
Health-related Quality of Life evaluation
Time frame: Baseline and 3 months follow up
Resource use of genetic screening
Time frame: 3 months follow up
Resource use of imaging screening
Time frame: 3 months follow up
Resource use (hospital visits)
Time frame: 3 months follow up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2021.
- Background: PubMed 30371227Mariscalco 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.
- Derived from this study: PubMed 35383466Abbasciano 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gavin J Murphy, Prof principal investigator
University of Leicester
Giovanni Mariscalco, Prof principal investigator
University of Leicester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing WES, MRI and TTE in people with Screening and Aortic Aneurysm and Dissection, run by University of Leicester at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of genetic diagnosis (time frame: Through study completion, an average of 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03861741, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2021; AzTrials last refreshed its copy on 6 Nov 2026.