Endothelial Modulation for Angiogenic Therapy

NCT00134433 | Completed Phase 1 DMC

• 1 other identifier: NA5163
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Coronary artery disease is the single most important killer of Canadians. Despite major advances in therapy, there is still a significant proportion of patients identified with the disease who die of it because current treatment approaches cannot effectively palliate their condition. A new treatment modality called therapeutic angiogenesis has appeared on the clinical research scene during the last five years; this approach recreates the natural processes of new blood vessel formation that is observed during growth and development in every human being. It is an extremely potent and promising modality, but so far the results of clinical trials in patients have been equivocal. One reason for the limited efficacy observed thus far with therapeutic angiogenesis may rest in that factors produced by the lining of the coronary arteries themselves are essential for angiogenic substances to take effect in the heart muscle of patients with severe coronary artery disease. These same patients, however, virtually all have, as a result of their disease, marked dysfunction of their coronaries and therefore fail to produce these factors in adequate quantities. This hypothesis has been verified with extensive animal data by the investigators of this research, where a swine model of coronary disease was shown to severely inhibit the action of angiogenic growth factors. If one wants angiogenesis to work, a means of improving the function of the coronary lining of patients with severe ischemic heart disease must be identified and its effects evaluated in order to allow for angiogenic substances to exert their action towards successful revascularization of the heart muscle. An amino acid called L-arginine has repeatedly been shown to markedly improve function of the coronary artery lining in patients with ischemic heart disease when administered regularly over a period of several months. This research will therefore test, in the form of a randomized clinical trial, whether this concomitant approach can make angiogenesis effective in patients with advanced coronary disease, by allowing for the action of growth factors to take place in the heart. If this approach is successful, as is anticipated, angiogenesis will constitute an effective modality for the treatment of coronary artery disease, not only in patients with advanced, severe involvement unamenable to any other form of cardiac therapy such as coronary artery bypass grafting, but even perhaps in all patients with coronary artery disease in need of revascularization. The goal of this investigation towards the making of a new, revolutionary, safe and efficacious modality for the treatment of the number one killer disease of Canadians is in complete agreement with the primary objective of the Heart and Stroke Foundation of Canada.

Conditions

Coronary Artery Disease

Keywords

Coronary Artery Disease, Diffuse; Coronary Artery Disease, Deemed Inoperable

Outcome Measures

Primary Outcomes (3)

• Blood flow to ischemic zone at 6 months compared to baseline: Persantine Ammonia Perfusion PET done at baseline prior to discharge from hospital and repeated at 3 months post intervention

• Echocardiogram done at baseline prior to discharge from hospital and repeated at 3 months post intervention

• Freedom from angina recurrence: Study participant interview and Seattle Angina Questionnaire administered (3 months, 6 months, 1 year). Results compared from preoperative baseline.

Interventions

intramyocardial VEGF angiogenesis (at a dose of 2 mg) GENETIC

oral L-arginine supplementation (at a dose of 6 g/day) DRUG

Eligibility Criteria

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

You may qualify if:

• Severe chronic angina
• Multi-vessel coronary artery disease
• Diffusely diseased left anterior descending coronary artery (LAD)
• At least 18 years of age at the time of written informed consent

You may not qualify if:

• Pregnancy, lactation, or any child-bearing potential
• Patients who are candidates for percutaneous transluminal coronary angioplasty (PTCA) or stenting
• Severe left ventricular dysfunction (ejection fraction \< 30%)
• Threatened proximal coronary occlusion or unstable angina
• Recent myocardial infarction (\< 1 month)
• Chronic renal failure (serum creatinine \> 130 µmol/L)
• Hepatic insufficiency (Child-Pugh Class C)
• Clinically significant valvular heart disease
• Personal history of neoplasia
• Abnormal serum prostate-specific antigen (PSA), bowel neoplasia screening questionnaire, or updated mammography report (if female) - any test not performed within the last 6 months will be conducted prior to confirmation of eligibility
• Family history of cancer (i.e. ≥ 2 first-degree relatives)
• History of diabetic retinopathy
• Latent herpes infection
• Schizophrenia
• Claustrophobia

Sponsors & Collaborators

• Ottawa Heart Institute Research Corporation: lead
• Heart and Stroke Foundation of Ontario: collaborator

Study Sites (1)

Division of Cardiac Surgery, University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

MeSH Terms

Conditions

Coronary Artery Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• Marc Ruel, MD MPH FRCSC

  Ottawa Heart Institute Research Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: August 22, 2005
• First Posted: August 24, 2005
• Study Start: November 1, 2004
• Primary Completion: March 1, 2007
• Study Completion: October 1, 2007
• Last Updated: June 21, 2012

Record last verified: 2012-06

Locations

CA (1)