Matrix Metalloproteinases Expression in the Neointimal Hyperplasia Induced by Drug Eluting Stent (DES) Implantation

NCT03375528 | Unknown DMC

• 1 other identifier: DankookMMP
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

If intimal growth is such that the initial lumen is narrowed significantly, distal blood flow is restricted and chronic tissue ischemia results. This occurs in native coronary arteries and during restenosis after coronary angioplasty or failure of some coronary vein grafts. Stent implantation has become the principal revascularization technique for coronary artery disease. But, in-stent restenosis (ISR) by neointimal hyperplasia persists as a significant limitation of this procedure in the era of drug eluting stent (DES). Coronary intervention might induce an inflammatory response by arterial wall damage, release of inflammatory and chemoattractant factors resulting in leukocyte and platelet activation. Then, Migration and proliferation of neointimal smooth muscle cells together with the deposition of extracellular matrix might lead to the development of ISR. It is known that matrix metalloproteinases (MMPs) play a key role in the pathogenesis of restenosis by controlling extracellular matrix degradation and the release of matrix-degrading MMPs, including MMP -2 and MMP-9, which facilitate intimal remodeling after angioplasty. Previous studies showed that increased levels of MMPs in coronary arteries undergoing percutaneous intervention may be associated with vascular remodeling and restenosis by promoting migration of vascular smooth muscle cells. Recently, Gregory et al. demonstrated that elevated serum activities of MMP-2 and -9 are associated with dramatically increased restenosis rates after PCI with implantation of DES. In patients with DESs, determination of MMP levels might be useful for identification of patients who are at high risk for ISR. However, not much is known about the relationship between MMPs and neointimal hyperplasia in patients with DES. In this study, the serum activity of MMP-2 and 9 were investigated in patients who had undergone follow-up coronary angiography with intravascular ultrasound (IVUS), which performed at 9 months post-DES implantation. Our aim was to evaluate if individual or combined levels of MMPs were associated with increased neointimal hyperplasia volume, that is, to evaluate the relationship, correlation between the levels of MMPs and neointimal hyperplasia volume.

Conditions

Coronary Artery Disease; Stent Restenosis

Keywords

Matrix metalloproteinase; neointimal hyperplasia

Outcome Measures

Primary Outcomes (1)

• Matrix Metalloproteinase expression correlate with neointimal plaque volume measure by intravascular ultrasound at 12 months follow up coronary angiography

  Endogenous MMP-2 and MMP-9 were measured in serum using a standardized enzyme-linked immunosorbent assay (ELISA; R\&D systems). This system measures the endogenous activity of the specific MMPs. Neointimal plaque volume measure by intravascular ultrasound at 12 months follow up coronary angiography

  One time frame - MMP sampling at 12 month follow up coronary angiography.

Study Arms (1)

coronary artery disease patients

EXPERIMENTAL

To define the Matrix metalloproteinases expression level in the neointimal hyperplasia induced by DES implantation

Device: DES implantation

Interventions

DES implantation DEVICE

Coronary artery intervention using Drug eluting stent and Intravascular Ultrasound is performed.

Also known as: Intravascular Ultrasound

coronary artery disease patients

Eligibility Criteria

• Age: 20 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ischemic heart disease

You may not qualify if:

• Left main coronary artery disease (defined as a stenosis of \> 50%)
• Prior complex lesion morphologies (aorto-ostial, bifurcation with \>2.0 mm side branch, severe calcification, chronic total occlusion)
• Long lesion that require more than two stents
• Inflammatory conditions likely to be associated with an acute phase response, autoimmune and neoplastic disease
• Advanced liver disease, renal failure, and valvular heart disease
• If there was persistent cardiogenic shock, refractory pulmonary edema, or hemodynamic instability (blood pressure \<90/50 mmHg).

Sponsors & Collaborators

• Dankook University: lead

Related Publications (2)

• Katsaros KM, Kastl SP, Zorn G, Maurer G, Wojta J, Huber K, Christ G, Speidl WS. Increased restenosis rate after implantation of drug-eluting stents in patients with elevated serum activity of matrix metalloproteinase-2 and -9. JACC Cardiovasc Interv. 2010 Jan;3(1):90-7. doi: 10.1016/j.jcin.2009.10.023.

  PMID: 20129576 BACKGROUND

• Schoenhagen P, Vince DG, Ziada KM, Kapadia SR, Lauer MA, Crowe TD, Nissen SE, Tuzcu EM. Relation of matrix-metalloproteinase 3 found in coronary lesion samples retrieved by directional coronary atherectomy to intravascular ultrasound observations on coronary remodeling. Am J Cardiol. 2002 Jun 15;89(12):1354-9. doi: 10.1016/s0002-9149(02)02346-9.

  PMID: 12062727 BACKGROUND

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Ultrasonography, Interventional

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Ultrasonography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Tae Soo Kang, PhD

  Dankook University Hospital 201 Manghyanro, Dongnam-gu, Cheonan-si, Chunchungnam-do, 31116, Republic of Korea

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tae Soo Kang, PhD

CONTACT

821093599160; neosoo70@dankook.ac.kr

Sung Soo Cho, MD

CONTACT

821088666875; drsscho@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Patients derived from a population of patients referred to 12 months follow-up coronary angiography for ischemic heart disease who are enable to be performed IVUS will be enrolled in the present trial, between December 2017 and December 2018. The study was an all comers design involving consecutive enrollment of patients with stable angina or acute coronary syndrome who had at least 1 coronary lesion (defined as a stenosis of \>50%) suitable for stent implantation 12 months before. The follow-up coronary angiography was performed according to standard techniques by experienced interventionalists only. Instent restenosis was defined as a diameter stenosis ≥50% of the vessel reference diameter by visual assessment. Detailed demographic details including anthropometric measurements, cardiovascular risk factors and medication use were recorded for the participants.

Study Record Dates

• First Submitted: November 20, 2017
• First Posted: December 18, 2017
• Study Start: January 1, 2018
• Primary Completion: January 1, 2019
• Study Completion: May 1, 2019
• Last Updated: December 18, 2017

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available within 1 year of study completion.
• Access Criteria: Data acess requests will be reviewed by an external independent Review Panel.