Soluble Receptors for Advanced Glycation End-Products and PCI

May 29, 2013 updated by: University of Saskatchewan

Soluble Receptors for Advanced Glycation End-Products to Predict the Type of Stent Implant

It is hypothesized that patients with low pre-PCI serum levels of sRAGE should receive DES implantation and/ or procedures taken to increase serum levels of sRAGE and/ or decrease the serum levels of AGE.

The purpose of this pilot study is to afford invasive cardiologists with additional evidenced based information to guide their decision as to which patients should receive a BMS or DES for coronary implantation.

The objectives of the study are to determine whether or not:

  1. Patients with low pre-PCI serum levels of sRAGE who receive bare metal stents develop restenosis
  2. Patients with high pre-PCI serum levels of sRAGE who receive bare metal stents will have reduced risk of the development of restenosis
  3. Patients with low pre-PCI serum levels of sRAGE who receive drug eluting stents will have an increased risk of the development of restenosis

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Advanced glycation end products (AGE) are irreversible adducts formed from the non-enzymatic glycation and oxidation of proteins, lipids and nucleic acids. 1-4 AGE interacts with three types of cell receptors for advanced glycation end products (RAGE) namely full-length RAGE, N-truncated and C-truncated soluble receptors for AGE (sRAGE). The interaction of full-length RAGE with AGE increases the expression of adhesion molecules, including soluble vascular cell adhesion molecule-1 (sVCAM-1) and the cytokine tumor necrosis factor-α (TNF- α) activation of nuclear factor kappa B (NFκB) which in turn increases the expression of proinflammatory genes for adhesion molecules and cytokines, and the generation of reactive oxygen species (ROS). The function of N-truncated RAGE is poorly understood. sRAGE is not membrane bound and circulates in the plasma. Acting as a decoy for RAGE ligands (AGE), sRAGE competes with full-length RAGE for ligand binding. Consequently, sRAGE plays a protective role by preventing activation of full-length RAGE.

Adhesion molecules, cytokines, and ROS are involved in the development and progression of atherosclerosis and lesion instability. The AGE and RAGE axis is involved in the development atherosclerosis in diabetes. Balloon injury in carotid artery and endothelial denudation in animal models increases the levels of RAGE and AGE in the arterial wall and produce neointimal hyperplasia. Treatment with sRAGE in animal models reduces neointimal growth, decreases smooth muscle cell proliferation and migration, and expression of extracellular matrix. sRAGE reduces the atherosclerotic lesions in Apo-E -/- mice and this effect is associated with a decrease in aortic VCAM-1 and tissue factor.

Recently, we have demonstrated that the levels of serum sRAGE are lower while the serum levels of AGE, sVCAM-1 and TNF-α are higher in subjects with NSTEMI as compared to healthy controls 31. Furthermore, we have shown that the NSTEMI patients, who underwent PCI with BMS implantation and developed post-PCI restenosis after six-months, had lower serum levels of sRAGE as compared to those who did not 30. In the proposed study we expect to find that all patients with very low levels of serum sRAGE receiving either a BMS develop post-PCI restenosis while patients with very low serum levels of sRAGE receiving DES will increased rate of post-PCI restenosis. In addition, those patients with high levels of sRAGE who receive either BMS or DES will have a reduced rate of restenosis.

This study has clinical significance because in our previous study (McNair et al, 2010), we demonstrated that low serum levels of sRAGE are associated with 100% restenosis following BMS implantation. In these situations DES implantation will be highly beneficial.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 0W8

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with NSTEMI
  • Discrete denovo localized lesions in single or multiple vessel
  • Non-diabetic
  • EF> 40%
  • Patients willing to come back for a follow-up angiogram 6 months post -PCI

Exclusion Criteria:

  • The reference diameter artery less than 2.5 mm in diameter
  • STEMI
  • Post-coronary artery bypass graft surgery
  • Diabetic
  • Coexisting inflammatory diseases
  • Coexisting valvular disease
  • Patients with a history of substance abuse

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Bare Metal stent
Stent that has not been impregnated with an anti-restenotic drug
Other: Bare Metal Stent
Active Comparator: Drug Eluting Stent
Stent that has been impregnated with an anti-restenotic drug
Other: Drug Eluting Stent
Comparison of two stents to see which results in best outcome.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
sRAGE
Time Frame: 6-months
The serum levels of sRAGE will be determined at six months.
6-months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
coronary restenosis
Time Frame: 6-months
The patient will have a followup angiogram to determine if restenosis is present.
6-months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Saskatchewan

Investigators

  • Principal Investigator: Erick McNair, PhD, University of Saskatchewan

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2013

Primary Completion (Anticipated)

March 1, 2015

Study Completion (Anticipated)

June 1, 2015

Study Registration Dates

First Submitted

May 29, 2013

First Submitted That Met QC Criteria

May 29, 2013

First Posted (Estimate)

June 3, 2013

Study Record Updates

Last Update Posted (Estimate)

June 3, 2013

Last Update Submitted That Met QC Criteria

May 29, 2013

Last Verified

March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5516

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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