Angiogenesis Using VEGF-A165/bFGF Plasmid Delivered Percutaneously in No-option CAD Patients; a Controlled Trial

Summary

Achieving therapeutic angiogenesis with gene therapy using a plasmid coding human VEGF-A165/bFGF injected into ischemic myocardium of refractory coronary artery disease patients, employing a percutaneous catheter-based technique- a double-blind placebo controlled study.

Some patients with persistent coronary artery disease cannot be effectively treated using methods available today ("no-option" patients). It is currently evident that an emerging therapy for them might be the stimulation of neoangiogenesis in the area of ischemic myocardium using growth factor genes. Agents attracting greatest interest are FGF (fibroblast growth factor) and VEGF (vascular-endothelial growth factor). A number of methods have been tested to deliver these agents to the area of interest.

Basic research has revealed that potent forms of angiogenic growth factors are the basic FGF (bFGF) and VEGF type A. Most clinical research on therapeutic angiogenesis is done using one of these two growth factors. This is to our knowledge the first clinical study using bicistronic VEGF-A 165/bFGF plasmid.

Patient population will comprise CCS III and CCS IV coronary artery disease patients who cannot be treated with standard revascularization methods. In the course of study we shall attempt to analyze the efficacy of therapeutic plasmid-induced angiogenesis in terms of myocardial perfusion increase and clinical symptom improvement. The feasibility and safety of plasmid delivery method will also be assessed. A percutaneous catheter-based technique (Myo-Star, Johnson \& Johnson®) is used for plasmid delivery.

All patients enrolled will receive optimal medical treatment as judged by treating physician. An effort will be made to modify medical therapy during the study course only for clear reasons.

Standard angiography and ventriculography will be performed prior to plasmid injection therapy. Ischemic area of interest will be identified on inclusion by SPECT. Cardiac nuclear magnetic resonance (cNMR) with adenosine will also be performed to assess heart morphology, function and perfusion. Next, injections will be performed according to protocol.

Follow-up visits will be performed at month 4 and month 12 after injection therapy.

A change in myocardial perfusion at rest and on dipyridamole-stress SPECT evaluation after injection therapy will be the primary measure of efficacy. Changes in exercise tolerance will also be monitored along with a number of other efficacy and safety parameters.

Conditions

• Coronary Artery Disease

Interventions

GENETIC

intramyocardial injection of VEGF-A165/bFGF:placebo plasmid

The plasmid will be given at a total dose of 0.5 mg, 10 injections of 0,2 ml each into the region of reversible ischemia. The process of injecting the solution into each of ten points within the ischemic zone will take 20 to 40 seconds to minimize muscle disruption

Sponsors & Collaborators

• Center of Oncology, Warsaw, Poland

  collaborator UNKNOWN

• Medical University of Warsaw

  collaborator OTHER

• Ministry of Scientific Research and Information Technology, Poland

  collaborator OTHER_GOV

• Polpharma Foundation for Development of Polish Pharmacy and Medicine

  collaborator UNKNOWN

• National Institute of Cardiology, Warsaw, Poland

  lead OTHER

Principal Investigators

• Witold Ruzyllo, Prof. · National Institute of Cardiology, Warsaw, Poland

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2004-12-31

Primary Completion

2008-05-31

Completion

2009-05-31

Countries

• Poland

Study Locations