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

This study has been completed.
Sponsor:
Collaborators:
Center of Oncology, Warsaw, Poland
Medical University of Warsaw
Ministry of Scientific Research and Information Technology, Poland
Polpharma Foundation for Development of Polish Pharmacy and Medicine
Information provided by:
Institute of Cardiology, Warsaw, Poland
ClinicalTrials.gov Identifier:
NCT00620217
First received: February 4, 2008
Last updated: November 27, 2009
Last verified: November 2009
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease
Genetic: intramyocardial injection of VEGF-A165/bFGF:placebo plasmid
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Therapeutic Angiogenesis Using Human VEGF-A165/bFGF Plasmid Injected Percutaneously Into the Ischemic Myocardium of "No-option" Coronary Artery Disease Patients; Double-blind Placebo Controlled Study

Resource links provided by NLM:


Further study details as provided by Institute of Cardiology, Warsaw, Poland:

Primary Outcome Measures:
  • Change in myocardial perfusion at rest and on dipyridamole-stress SPECT evaluation at month 4 after injection therapy [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in exercise tolerance [ Time Frame: month 4 and 12 ] [ Designated as safety issue: No ]
  • Changes in life quality and patient's clinical condition [ Time Frame: month 4 and 12 ] [ Designated as safety issue: Yes ]
  • Angiographic changes [ Time Frame: 4 months ] [ Designated as safety issue: No ]
  • The occurrence of major cardiac adverse events (MACE) during long-term follow-up [ Time Frame: throughout the 1-year follow-up ] [ Designated as safety issue: Yes ]
  • Serum VEGF-A165 and bFGF level [ Time Frame: week 1,2,4,8 ] [ Designated as safety issue: No ]
  • The occurrence of adverse events related to the plasmid administration procedure [ Time Frame: Hospitalization related to procedure ] [ Designated as safety issue: Yes ]
  • occurrence of adverse events that may be related to overt VEGF or FGF activity [ Time Frame: throughout the 1-year follow-up ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 52
Study Start Date: December 2004
Study Completion Date: May 2009
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
intramyocardial injection of bicistronic VEGF-A165/bFGF plasmid
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
Placebo Comparator: 2
intramyocardial injection of placebo plasmid
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Severe (>= CCS III) ischemic heart disease despite optimal medical treatment in patients not amenable to percutaneous transluminal coronary angioplasty or coronary artery bypass surgery
  • Left ventricular ejection fraction >35%
  • Significant stress-induced reversible ischemic area documented on dipyridamole stress myocardial perfusion scintigraphy
  • Able to understand and willing to sign the informed consent
  • Older than 18 years of age

Exclusion Criteria:

  • Angina <CCS III
  • Secondary angina
  • Acute myocardial infarction within 4 weeks prior to inclusion
  • Diabetes with proliferative retinopathy
  • Diagnosed or suspected tumor
  • Chronic inflammatory or autoimmune disease
  • Fertile women
  • Left ventricular ejection fraction <35%
  • Patients not willing to or not able to give the informed consent to participate in the study
  • Patients with a severe disease (other than CAD) having life-expectancy below 1 year
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00620217

Locations
Poland
Institute of Cardiology
Warsaw, Poland, 04-628
Sponsors and Collaborators
Institute of Cardiology, Warsaw, Poland
Center of Oncology, Warsaw, Poland
Medical University of Warsaw
Ministry of Scientific Research and Information Technology, Poland
Polpharma Foundation for Development of Polish Pharmacy and Medicine
Investigators
Principal Investigator: Witold Ruzyllo, Prof. Institute of Cardiology, Warsaw, Poland
  More Information

Publications:
Kukula, K., Dabrowski, M., Chojnowska, L., Chmielak, Z., Witkowski, A., Skwarek, M., Kadziela, J., Malecki, M., Teresinska, A., Kownacki, L., Piotrowska-Kownacka, D., Ruzyllo, W., Theoretical base and investigational plan of the VIFCAD study- gene therapy for refractory coronary artery disease in no-option patients using transendocardial bicistronic VEGF/FGF plasmid injection. Post Kardiol Interw; 2, 1 (2006) 116-123

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof. Witold Ruzyllo, Institute of Cardiology, Warsaw, Poland
ClinicalTrials.gov Identifier: NCT00620217     History of Changes
Other Study ID Numbers: PBZ-KBN-099/P05/01
Study First Received: February 4, 2008
Last Updated: November 27, 2009
Health Authority: Poland: Ministry of Science and Higher Education

Keywords provided by Institute of Cardiology, Warsaw, Poland:
heart ischemia
coronary artery disease
plasmid
VEGF
FGF
percutaneous
gene therapy
SPECT
nuclear magnetic resonance

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on September 16, 2014