Influence of Statins in Artery Aneurysms

NCT ID: NCT03061487

Last Updated: 2017-02-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

20 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-02-15

Study Completion Date

2018-04-27

Brief Summary

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The altered balance between the proteinases and their tissue inhibitors (TIMPS) is one of the pathogenetical mechanism of the aneurysmatic connective tissue degeneration. The increasement of protease, collagenase and elastase activity results indeed in a dramatic drop of collagen and elastin tissue and serum levels.Matrix Metalloproteinases (MMPs) are a group of proteolytic enzymes that along with their specific and non-specific inhibitors modulate the extracellular matrix composition. Recent studies have suggested an interesting role of microRNAs (miRNAs) in the regulation mechanisms of inflammation.

The aim of our study is to analyse the influence of statin treatment on aneurysmatic disease by monitoring MMPs and miRNAs in aneurysmatic wall tissue and MMps blood levels.

Detailed Description

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The altered balance between the proteinases and their tissue inhibitors (TIMPS) is one of the pathogenetical mechanism of the aneurysmal connective tissue degeneration. The increase of protease, collagenase and elastase activity results indeed in a dramatic drop of collagen and elastin tissue and serum levels.

Vessels wall strength decrease is associated with the blood flow shear stress and affects negatively the walls integrity, causing the aneurysmatic vessel degeneration.

Matrix Metalloproteinases (MMPs) are a group of proteolytic enzymes that along with their specific and non-specific inhibitors modulate the extracellular matrix composition.

So far, 25 MMPs have been discovered, in particular, the ones that will be considered in this study are: MMP-2, MMP-9, and neutrophil gelatinase-associated lipocalin (NGAL) a related protein which is able to control MMP-9 activities.

Inflammation plays a central role in the pathogenetical pathway of aneurysmatic developement. Recent studies have suggested an interesting role of miRNAs in the regulation mechanisms of inflammation. miRNAs are short ribonucleic acid molecules usually composed of 20 to 25 nucleotides that can regulate mRNA transcription and protein translation by targeting the 3'-untranslated regions (3'-UTR) of target genes. miRNAs are involved in various physiological responses and pathological processes. Increasing evidence suggest that miRNAs are involved in inflammatory responses. In particular the ones that will be focused on this study are: miR-29b, miR-21, miR-181a, miR-150.

Very often, patients with aneurysmatic disease are under statin treatment. Some Statins (Atorvastatin, Simvastatin or Rosuvastatin) with pleiotropic effects may also play a protective role by conditioning the progression of the aneurysmatic degeneration.

The aim of our study is to analyse the influence of statin treatment on aneurysmatic disease by monitoring some MMPs and related molecules (MMP-2, MMP-9 and NGAL), miRNAs (the evaluation will be performed in aneurysmatic wall tissues and circulating blood levels).

Patients affected by central and peripheral aneurysmatic disease will be recruited and then divided in two groups based on the dosage of the statin treatment: the first group with maximum statin daily dose (Atorvastatin 80 mg, Simvastatin 40 mg, Rosuvastatin 40 mg), the second group with minimum statin daily dose. The latter will be defined as the control group.

Only patients which will fullfill the criteria to undergo surgical treatment will be recruited in the study in order to collect biological specimen of the aneurysmatic tissues .

The investigation consist in:

* taking a preoperative blood sample to evaluate the MMPs circulating levels
* taking an aneurysmatic vessel wall histological sample with an intraoperative biopsy to evaluate the tissue MMPs and miRNAs levels.

Previously, several studies suggested a role of MMPs (MMP-2 and MMP-9) and miRNAs in regulation of aneurysm developement, in particular miR29b, miR-181a, miR-21, miR-150.

The comparison between MMPs Levels in the study group and in the control group might highlight a role for MMPs level as a marker of aneurysmatic disease progression, consequently allowing the patient's stratification by analysing the risk of aneurysmatic evolution and growth.

Conditions

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Statin Aneurysm Extracellular Matrix Alteration

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Group I

Patients affected by central and peripheral aneurismatic disease with maximum statin daily dose ( Atorvastatin 80 mg, Simvastatin 40 mg, Rosuvastatin 40 mg).

Patients will undergo Open Surgical Treatment of Aneurysm (Aneurysmectomy).

The investigation consist in:

* taking a preoperative blood sample to evaluate the MMPs circulating levels
* taking an aneurismatic vassel wall istological sample with an intraoperative biopsy to evaluate the tissue MMPs and miRNAs levels

Open Surgical Treatment of Aneurysm (Aneurysmectomy)

Intervention Type PROCEDURE

Aneurysmectomy is a surgical procedure in which a localized, dilated, weakened section of an artery (aneurysm) is removed (resected). The artery is either replaced with a synthetic graft, as seen in an aneurysm in the chest (thoracic aneurysm), abdomen (abdominal aneurysm) or leg (femoral or popliteal aneurysm).

Group II

Patients affected by central and peripheral aneurismatic disease with minimum statin daily dose.

Patients will undergo Open Surgical Treatment of Aneurysm (Aneurysmectomy).

The investigation consist in:

* taking a preoperative blood sample to evaluate the MMPs circulating levels
* taking an aneurismatic vassel wall istological sample with an intraoperative biopsy to evaluate the tissue MMPs and miRNAs levels

Open Surgical Treatment of Aneurysm (Aneurysmectomy)

Intervention Type PROCEDURE

Aneurysmectomy is a surgical procedure in which a localized, dilated, weakened section of an artery (aneurysm) is removed (resected). The artery is either replaced with a synthetic graft, as seen in an aneurysm in the chest (thoracic aneurysm), abdomen (abdominal aneurysm) or leg (femoral or popliteal aneurysm).

Interventions

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Open Surgical Treatment of Aneurysm (Aneurysmectomy)

Aneurysmectomy is a surgical procedure in which a localized, dilated, weakened section of an artery (aneurysm) is removed (resected). The artery is either replaced with a synthetic graft, as seen in an aneurysm in the chest (thoracic aneurysm), abdomen (abdominal aneurysm) or leg (femoral or popliteal aneurysm).

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Patients under statins treatment with pleiotropic effect: Simvastatin, Rosuvastatin, Atorvastatin
* Patients underwent open aneurysm repair
* Age \>18
* signing informed consent

Exclusion Criteria

* Patients with chronic diseases such as liver diseases
* Pazient whith malignant diseases
* Recreational drug intake and alcohol abuse
* Intake of statins other than those under study or in combination therapy
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Catanzaro

OTHER

Sponsor Role lead

Responsible Party

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Prof. Raffaele Serra, MD, Ph.D.

Associate Professor of Vascular Surgery

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Stefano de Franciscis, M.D.

Role: STUDY_CHAIR

University Magna Graecia of Catanzaro

Locations

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University Magna Graecia of Catanzaro

Catanzaro, Catanzaro, Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Raffaele Serra, M.D.; Ph.D.

Role: CONTACT

+39 09613647380

Luca Gallelli, M.D.; Ph.D.

Role: CONTACT

+39 0961 3339245656

Facility Contacts

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Raffaele Serra, M.D., Ph.D.

Role: primary

+3909613647380

References

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Serra R, Grande R, Montemurro R, Butrico L, Calio FG, Mastrangelo D, Scarcello E, Gallelli L, Buffone G, de Franciscis S. The role of matrix metalloproteinases and neutrophil gelatinase-associated lipocalin in central and peripheral arterial aneurysms. Surgery. 2015 Jan;157(1):155-62. doi: 10.1016/j.surg.2014.06.008. Epub 2014 Nov 1.

Reference Type BACKGROUND
PMID: 25444221 (View on PubMed)

de Franciscis S, Mastroroberto P, Gallelli L, Buffone G, Montemurro R, Serra R. Increased plasma levels of metalloproteinase-9 and neutrophil gelatinase-associated lipocalin in a rare case of multiple artery aneurysm. Ann Vasc Surg. 2013 Nov;27(8):1185.e5-7. doi: 10.1016/j.avsg.2013.01.011. Epub 2013 Aug 26.

Reference Type BACKGROUND
PMID: 23988549 (View on PubMed)

Serra R, Volpentesta G, Gallelli L, Grande R, Buffone G, Lavano A, de Franciscis S. Metalloproteinase-9 and neutrophil gelatinase-associated lipocalin plasma and tissue levels evaluation in middle cerebral artery aneurysms. Br J Neurosurg. 2014 May 5. doi: 10.3109/02688697.2014.913777. Online ahead of print.

Reference Type BACKGROUND
PMID: 24799278 (View on PubMed)

Piechota-Polanczyk A, Demyanets S, Mittlboeck M, Hofmann M, Domenig CM, Neumayer C, Wojta J, Klinger M, Nanobachvili J, Huk I. The Influence of Simvastatin on NGAL, Matrix Metalloproteinases and Their Tissue Inhibitors in Human Intraluminal Thrombus and Abdominal Aortic Aneurysm Tissue. Eur J Vasc Endovasc Surg. 2015 May;49(5):549-55. doi: 10.1016/j.ejvs.2015.02.011. Epub 2015 Mar 21.

Reference Type BACKGROUND
PMID: 25800096 (View on PubMed)

Maegdefessel L, Azuma J, Toh R, Merk DR, Deng A, Chin JT, Raaz U, Schoelmerich AM, Raiesdana A, Leeper NJ, McConnell MV, Dalman RL, Spin JM, Tsao PS. Inhibition of microRNA-29b reduces murine abdominal aortic aneurysm development. J Clin Invest. 2012 Feb;122(2):497-506. doi: 10.1172/JCI61598. Epub 2012 Jan 24.

Reference Type BACKGROUND
PMID: 22269326 (View on PubMed)

Adam M, Raaz U, Spin JM, Tsao PS. MicroRNAs in Abdominal Aortic Aneurysm. Curr Vasc Pharmacol. 2015;13(3):280-90. doi: 10.2174/15701611113119990015.

Reference Type BACKGROUND
PMID: 23713862 (View on PubMed)

Other Identifiers

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ER.ALL.2016.04

Identifier Type: -

Identifier Source: org_study_id

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