Stem Cell Mobilization and VEGF Gene Transfer for Heart Failure
The purpose of this study is to evaluate the safety and bioactivity of intramyocardial gene transfer using VEGF (vascular endothelial growth factor) in patients with ischemic heart failure. The research treatment of this CHF study will involve the use of an intramuscular injection with a catheter inserted in through the groin to transfer a type of DNA (phVEGF165 gene) to the wall of the heart. Genes (which are part of the DNA molecules) carry instructions to allow the cells to produce specific proteins. Gene transfer or treatment with DNA (a necessary part of all cells) is being studied for the treatment of patients with heart failure. This research therapy, which is experimental and not proven, is designed to try to grow new blood vessels to improve blood flow to areas of the heart that are not receiving enough blood.
DNA is present in all cells and provides the instructions for making proteins. After delivering a piece of DNA containing the vascular endothelial growth factor 1 (VEGF-1) gene (the product being studied) into cells, the cells may produce a specific protein called vascular endothelial growth factor 1 (VEGF-1). Animal studies have indicated that the VEGF-1 protein may cause new blood vessels to grow. The Vascular Endothelial Growth Factor Gene (ph VEGF 165) is found on the VEGF DNA. Experiments performed in animals show that once in the heart wall, the DNA directs the cells of the heart muscle to make the VEGF protein. VEGF 165 is a protein that has been shown to stimulate cells (known as endothelial cells), which form the inner lining of blood vessels. This protein causes cells to divide and grow, thereby forming new blood vessels. It is anticipated that this new blood supply may help the heart pump the blood more effectively and relieve some heart failure symptoms. We do not yet have enough information to know what will happen in humans, that is why we are doing this research.
After gene transfer we will begin a process to help move some of the stem cells from the bone marrow into the blood circulation. Subjects will be given the drug called G-CSF (a drug used to move cells from the bone marrow into the blood stream). Stem cells are young cells produced by bone marrow (the spongy cavity in the center of large bones) that can develop into blood cells or other types of cells. This medication triggers the movement of stem cells out of the bone marrow and into the blood stream. Before being released into the blood stream, stem cells receive signals that direct them to become specific types of cells such as CD34+ cells (endothelial progenitor cells). CD34+ cells that move to or are in the area of damaged heart tissue may promote growth of new blood vessels that supply blood and nutrients and thereby improve the chance of survival of heart tissue, improve heart function, and possibly have a long-term benefit.
We will be recruiting 12 subjects for this study. There will be no randomization and no placebo group. Once eligibility in the research study has been determined all subjects will be treated with the VEGF and G-CSF.
Ischemic Congestive Heart Failure (CHF)
Genetic: Vascular Endothelial Growth Factor (VEGF1)
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||phVEGF165 GENE TRANSFER TO PROMOTE ANGIOGENESIS IN PATIENTS WITH ISCHEMIC HEART FAILURE|