Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03061487
Other study ID # ER.ALL.2016.04
Secondary ID
Status Recruiting
Phase N/A
First received February 15, 2017
Last updated February 23, 2017
Start date February 15, 2017
Est. completion date April 27, 2018

Study information

Verified date February 2017
Source University of Cantanzaro
Contact Raffaele Serra, M.D.; Ph.D.
Phone +39 09613647380
Email rserra@unicz.it
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

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.


Description:

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.


Recruitment information / eligibility

Status Recruiting
Enrollment 20
Est. completion date April 27, 2018
Est. primary completion date February 26, 2018
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Procedure:
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).

Locations

Country Name City State
Italy University Magna Graecia of Catanzaro Catanzaro

Sponsors (1)

Lead Sponsor Collaborator
University of Cantanzaro

Country where clinical trial is conducted

Italy, 

References & Publications (6)

Adam M, Raaz U, Spin JM, Tsao PS. MicroRNAs in Abdominal Aortic Aneurysm. Curr Vasc Pharmacol. 2015;13(3):280-90. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Serra R, Grande R, Montemurro R, Butrico L, Caliò 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. — View Citation

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. [Epub ahead of print] — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Evaluation of MMP-2, MMP-9 and NGAL levels in blood and aneurysms tissue MMP-2, MMP-9 and NGAL will be studied in both groups. Elisa Testing will be used to analyze the blood samples and Western blot analysis will be used for the tissue samples. 1 year
Primary Evalutation of miRNAs levels in blood and aneurysms tissue Evaluation of miRNAs levels (in particular miR29b, miR-181a, miR-21, miR-150) will be studied in both groups. Stem-loop reverse-transcription PCR (RT-qPCR) method will be used for measuring individual microRNAs (miRNAs) in tissue and blood samples. 1 year
See also
  Status Clinical Trial Phase
Not yet recruiting NCT06235619 - Arch Size Study for Anatomical Variations
Completed NCT01178710 - Effect of Simvastatin on Cardiac Function N/A
Not yet recruiting NCT00905931 - Lycopene Following Aneurysmal Subarachnoid Haemorrhage Phase 2
Completed NCT00349908 - A Feasibility Study of the Cordis Neurovascular Self Expanding Stent System in Intracranial Arteries Phase 1
Recruiting NCT03285100 - The Effects of Discontinuation of Vitamin K Antagonists on the Rate of Elastin Degradation N/A
Recruiting NCT06189950 - Registration Trial of the Intracranial Visualized Stent for the Wide-necked Intracranial Aneurysms:REBRIDGE N/A
Active, not recruiting NCT04592185 - The Study of the Fenestrated Anaconda Device in the Treatment of Abdominal Aortic Aneurysms
Completed NCT01970605 - Silver Graft All Comers Registry
Completed NCT00282893 - Balloon Prophylaxis of Aneurysmal Vasospasm Phase 2
Active, not recruiting NCT00549380 - Clinical Study of Aneurysm Exclusion Phase 1
Completed NCT04598802 - COvera in BRAnch Registry
Completed NCT04246125 - Patient Skin Dose in Interventional Radiology
Recruiting NCT05829746 - PROSPECTIVE, MULTI-CENTER, OPEN-LABEL, SINGLE-ARM REGISTRATION TRIAL OF THE TUBRIDGE FOR THE TREATMENT OF WIDE-NECKED SMALL AND MEDIUM-SIZED INTRACRANIAL ANEURYSMS N/A
Completed NCT03242343 - VasQ External Support for Arteriovenous Fistula N/A
Recruiting NCT02878967 - Standardized Long Term Follow-up of Patients After Endovascular Embolization of a Brain Aneurysm
Active, not recruiting NCT02345005 - Iliac Branch Excluder ReGistry (IceBERG)
Recruiting NCT02167997 - EffectiveNess and SAfety of Small ANeurysm COiling Trial N/A
Recruiting NCT00549016 - Clinical Study of Aneurysm Exclusion N/A
Completed NCT02848612 - Evaluation of the Amiens University Hospital Neuroradiology Anticoagulation Protocol
Enrolling by invitation NCT04269447 - Prospective Aortic Biobank of POP-STAR