Abdominal aortic aneurysm (AAA) is an aortic dilatation superior or equal to 30 mm with an estimated prevalence at 8% in men over 65 year-old. It evolves with no clinical signal until the rupture of the aortic wall with dramatic outcomes. The pathophysiological mechanisms include extracellular matrix remodeling, smooth muscle cells apoptosis, aggregation and activation of inflammatory cells in the aortic wall and heredity. The initiating and regulatory processes are complex and not fully elucidated. They encompass local aortic environment (flux, thrombus, wall shear stress, pressure and adipose tissue) and patient-dependent genetic (de)regulation.
This project follows the previous prospective ACTA study that aimed at identifying clinical criteria, circulating biomarkers or imaging data for thoracic aneurysm prognosis in an AAA population. The preliminary results showed that 1) a low wall shear stress index and the luminal volume are more predictive values for a rapid AAA growth and an intraluminal thrombus than the maximal aortic diameter 2) three thoracic aortic phenotypes (normal, dilated, aneurysmal) stratify the disease extent 3) the age and the female gender are associated to an extended disease. During this study we created a biobank in which blood samples of AAA patients were collected at the time of their inclusion (T1). This new ACTA-miRNA study aims at correlating circulating biomarkers to the anatomical and biomechanical markers previously highlighted for a rapid aneurysmal growth. Circulating miRNA are involved in parietal remodeling and constitute promising targets for estimating patients-specific aortic risk.
From the literature, we thus selected 18 miRNA described to be involved in AAA biology: inflammation, remodeling, cellular homeostasis and wall shear stress. As control, we select non-AAA patients presenting with peripheral arterial obstructive disease (PAOD) matched in age, BMI, tobacco consumption, diabetes, cholesterol level and blood pressure with AAA patients enrolled in the ACTA study. During their follow-up, these ACTA patients are solicited to continue the program research and can participate to the ACTA-miRNA study. A third time analysis is performed for them (T3): we collect imaging data of total aorta required by their standard follow-up, as well as a blood sample. Differential analysis of the miRNA panel will be conducted between 1) AAA patients (T1) vs PAOD patients 2) fast-growing AAA vs slow-growing AAA 3) AAA & AAT patient group vs AAA alone and/or AAA & dilatation of thoracic aorta. 110 patients from the ACTA study are eligible to be included into the ACTA mi-RNA study. Inclusion of PAOD controls will be conducted until the number of 165 cases is reached (1:1.5 ratio).
Our primary objective is to validate a circulating-miRNA signature specific for abdominal aortic aneurysm.
Condition or disease | Intervention/treatment | Phase |
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Abdominal Aorta Aneurysm | Genetic: Tissue-library | Not Applicable |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 220 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Other |
Official Title: | Circulating microRNAs and Degenerative Abdominal Aorta Aneurysm: Diagnostic Specificity and Prognostic Value in Clinical Practice |
Actual Study Start Date : | October 2, 2018 |
Estimated Primary Completion Date : | October 1, 2020 |
Estimated Study Completion Date : | October 1, 2021 |
Arm | Intervention/treatment |
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Experimental: AAA patients
Patients with abdominal aortic aneurysm (AAA)
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Genetic: Tissue-library
circulating biomarkers (miRNA panel) analysis of blood samples
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Experimental: PAOD patients
patients with peripheral arterial obstructive disease (PAOD)
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Genetic: Tissue-library
circulating biomarkers (miRNA panel) analysis of blood samples
|
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
• Case AAA T3 : Patients included in the ACTA study. They benefited from aortic imaging assessment at times T1 and T2 and were not operated on AAA.
• AOMI Case Control : Patients referred for hospitalization or referred to vascular surgery for management of chronic peripheral claudication on AOMI not associated with aneuric aneurysm evolutionary or previously operated. They must benefit from a CT angiography of the aorta and lower extremity arteries as well as a cardiac ultrasound scan.
Exclusion Criteria:
patients presenting one of the following pathologies associated with a disruption of the activation of coagulation and / or inflammation (less than 6 weeks old):
Contact: Laurence Bal, MD | laurence.bal@ap-hm.fr |
France | |
Assistance Publique Hôpitaux de Marseille | Recruiting |
Marseille, France, 13005 | |
Contact: Laurence Bal, MD laurence.bal@ap-hm.fr |
Study Director: | Emilie Garrido Pradalié | Assistance Publique Hôpitaux de Marseille |
Tracking Information | |||||
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First Submitted Date ICMJE | June 3, 2019 | ||||
First Posted Date ICMJE | June 5, 2019 | ||||
Last Update Posted Date | June 5, 2019 | ||||
Actual Study Start Date ICMJE | October 2, 2018 | ||||
Estimated Primary Completion Date | October 1, 2020 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Comparison of AAA miRNAs vs AOMI miRNAs [ Time Frame: 24 months ] Analyze the diagnostic value of the 18 selected microRNAs circulating profile in degenerative aneurysmal aortic remodeling (patients with an abdominal aortic aneurysm (AAA)) in comparison with the circulating profile of the same 18 microRNAs panel in the atherosclerosis remodeling (patients with peripheral arterial occlusive disease (AOMI) without AAA)
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Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | No Changes Posted | ||||
Current Secondary Outcome Measures ICMJE | Not Provided | ||||
Original Secondary Outcome Measures ICMJE | Not Provided | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Circulating microRNAs and Degenerative Abdominal Aorta Aneurysm | ||||
Official Title ICMJE | Circulating microRNAs and Degenerative Abdominal Aorta Aneurysm: Diagnostic Specificity and Prognostic Value in Clinical Practice | ||||
Brief Summary |
Abdominal aortic aneurysm (AAA) is an aortic dilatation superior or equal to 30 mm with an estimated prevalence at 8% in men over 65 year-old. It evolves with no clinical signal until the rupture of the aortic wall with dramatic outcomes. The pathophysiological mechanisms include extracellular matrix remodeling, smooth muscle cells apoptosis, aggregation and activation of inflammatory cells in the aortic wall and heredity. The initiating and regulatory processes are complex and not fully elucidated. They encompass local aortic environment (flux, thrombus, wall shear stress, pressure and adipose tissue) and patient-dependent genetic (de)regulation. This project follows the previous prospective ACTA study that aimed at identifying clinical criteria, circulating biomarkers or imaging data for thoracic aneurysm prognosis in an AAA population. The preliminary results showed that 1) a low wall shear stress index and the luminal volume are more predictive values for a rapid AAA growth and an intraluminal thrombus than the maximal aortic diameter 2) three thoracic aortic phenotypes (normal, dilated, aneurysmal) stratify the disease extent 3) the age and the female gender are associated to an extended disease. During this study we created a biobank in which blood samples of AAA patients were collected at the time of their inclusion (T1). This new ACTA-miRNA study aims at correlating circulating biomarkers to the anatomical and biomechanical markers previously highlighted for a rapid aneurysmal growth. Circulating miRNA are involved in parietal remodeling and constitute promising targets for estimating patients-specific aortic risk. From the literature, we thus selected 18 miRNA described to be involved in AAA biology: inflammation, remodeling, cellular homeostasis and wall shear stress. As control, we select non-AAA patients presenting with peripheral arterial obstructive disease (PAOD) matched in age, BMI, tobacco consumption, diabetes, cholesterol level and blood pressure with AAA patients enrolled in the ACTA study. During their follow-up, these ACTA patients are solicited to continue the program research and can participate to the ACTA-miRNA study. A third time analysis is performed for them (T3): we collect imaging data of total aorta required by their standard follow-up, as well as a blood sample. Differential analysis of the miRNA panel will be conducted between 1) AAA patients (T1) vs PAOD patients 2) fast-growing AAA vs slow-growing AAA 3) AAA & AAT patient group vs AAA alone and/or AAA & dilatation of thoracic aorta. 110 patients from the ACTA study are eligible to be included into the ACTA mi-RNA study. Inclusion of PAOD controls will be conducted until the number of 165 cases is reached (1:1.5 ratio). Our primary objective is to validate a circulating-miRNA signature specific for abdominal aortic aneurysm. |
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Detailed Description | Not Provided | ||||
Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Not Applicable | ||||
Study Design ICMJE | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Other |
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Condition ICMJE | Abdominal Aorta Aneurysm | ||||
Intervention ICMJE | Genetic: Tissue-library
circulating biomarkers (miRNA panel) analysis of blood samples
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Study Arms ICMJE |
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
220 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | October 1, 2021 | ||||
Estimated Primary Completion Date | October 1, 2020 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE |
Inclusion Criteria: • Case AAA T3 : Patients included in the ACTA study. They benefited from aortic imaging assessment at times T1 and T2 and were not operated on AAA. • AOMI Case Control : Patients referred for hospitalization or referred to vascular surgery for management of chronic peripheral claudication on AOMI not associated with aneuric aneurysm evolutionary or previously operated. They must benefit from a CT angiography of the aorta and lower extremity arteries as well as a cardiac ultrasound scan. Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
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Listed Location Countries ICMJE | France | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT03974958 | ||||
Other Study ID Numbers ICMJE | 2018-12 | ||||
Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Responsible Party | Assistance Publique Hopitaux De Marseille | ||||
Study Sponsor ICMJE | Assistance Publique Hopitaux De Marseille | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE |
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PRS Account | Assistance Publique Hopitaux De Marseille | ||||
Verification Date | June 2019 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |