Clinical trial NCT02145533: Matrix Metalloproteinases (MMPs),Neutrophil Gelatinase-associated Lipocalin (NGAL) Tissue and Plasma Levels and Aneurysms
Official title: Evaluation of Plasma and Tissue Levels of Metalloproteinases and Neutrophil Gelatinase-associated Lipocalin in Arterial Aneurysms.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: MMPs and NGAL in Ruptured and Non-ruptured Aneurysms
Keywords: MMP
NGAL
Arterial Aneurysms
Lead sponsor: University of Catanzaro
Sponsor class: OTHER
First posted: 2014-05-23
Enrollment: 307
Sex: ALL
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with diagnosis of aneurysmal disease (central and peripheral, ruptured and non-ruptured).

Brief summary: An association between arterial aneurysms and matrix metalloproteinases (MMPs) has been described previously. MMPs regulate extracellular structural proteins and tissue remodeling. Neutrophil Gelatinase-associated Lipocalin (NGAL) is involved in the regulation of MMP activity. The aim of this work was to study the relationship between the levels of MMPs and NGAL and arterial aneurysms.

In a multicenter, open label, parallel groups, prospective study, patients with aneurysmal disease were divided into two groups: Group I (with ruptured aneurysm) and Group II (with non-ruptured aneurysm). Healthy volunteer patients were also enrolled and represented the control group (Group III).

The investigators enrolled 307 patients (Group I: 107, Group II: 200) with arterial aneurysm: 49 popliteal, 31 common femoral, 2 superficial femoral, 29 common iliac artery, 3 common carotid and 193 abdominal aorta. Finally, 11 healthy volunteer patients (9 males and 2 females, age range 40-70 year-old, median 56) were enrolled in Group III.

Elisa test and Western blot analysis revealed greater levels of immunoreactive MMP-9 and NGAL in all patients with ruptured aneurysms, both central and peripheral aneurysms, and in the aneurismal vessels.

These results provide important advances in the understanding of the natural history of arterial aneurysms. MMPs and NGAL play a role in development of arterial aneurysms and they may represent molecular markers for the prevention of aneurysmal rupture

Detailed description: In the present study, the analysis of MMPs levels in plasma and tissues in patients with aneurysmal lesions identified several patterns of protease activity. Levels of both MMP-9 and NGAL were increased in aneurismal vessels, while the patterns of MMP-9 and NGAL expression was very high in all patients with ruptured aneurysm, both central and peripheral. These results show: 1) the chronic and degenerative nature of the aneurysmal lesion which is associated with increased levels of inflammatory proteinases, like MMP-9; 2) the apparent pivotal role of MMP-9 and NGAL in the pathophysiologic processes which lead to the final stage of natural history of aneurysms; and 3) the ubiquitous distribution of MMP-9 and NGAL. The pattern increased expression of MMP-9 and NGAL appears to be specific for aneurysmal arteries and it is not dependent on the anatomic site of the lesion.

Eligibility criteria: Inclusion Criteria:

* Patients with the diagnosis of arterial aneurysmal disease

Exclusion Criteria:

* History of cancer
* Hepatic failure
* Infectious or autoimmune diseases
* Patients requiring endovascular treatment.

Primary outcomes:
measure: Evaluation of MMPs levels in ruptured and non-ruptured aneurysms
timeFrame: 52 months
measure: Evaluation of NGAL levels in ruptured and non-ruptured aneurysms
timeFrame: 52 months
Secondary outcomes:
Other outcomes:
Locations:
city: Catanzaro
country: Italy
facility: University of Catanzaro
Study officials:
affiliation: University Magna Graecia of Catanzaro
name: Stefano de Franciscis, M.D.
role: STUDY_CHAIR
affiliation: University Magna Graecia of Catanzaro
name: Raffaele Serra
role: PRINCIPAL_INVESTIGATOR
References: