THIS IS A SHANNON AWARD PROVIDING PARTIAL SUPPORT FOR THE RESEARCH PROJECTS THAT FALL SHORT OF THE ASSIGNED INSTITUTE'S FUNDING RANGE BUT ARE IN THE MARGIN OF EXCELLENCE. THE SHANNON AWARD IS INTENDED TO PROVIDE SUPPORT TO TEST THE FEASIBILITY OF THE APPROACH; DEVELOP FURTHER TESTS AND REFINE RESEARCH TECHNIQUES; PERFORM SECONDARY ANALYSIS OR AVAILABLE DATA SETS; OR CONDUCT DISCRETE PROJECTS THAT CAN DEMONSTRATE THE PI'S RESEARCH CAPABILITIES OR LEND ADDITIONAL WEIGHT TO AN ALREADY MERITORIOUS APPLICATION. THE ABSTRACT BELOW IS TAKEN FROM THE ORIGINAL DOCUMENT SUBMITTED BY THE PRINCIPAL INVESTIGATOR. DESCRIPTION: (Adapted from investigator's abstract) Pressure ulcers are major secondary complications in patients with spinal cord injuries and are associated with significant disability and financial burden. Treatment costs for pressure ulcers secondary to a spinal cord injury have been reported to be over $58,000 per ulcer. A large number of the pressure ulcers occurring secondary to spinal cord injury are chronic in nature failing to heal in an orderly and timely fashion and to sustain restoration of structure or function after healing. A major goal of our research is to identify factors that enhance the healing of chronic pressure ulcers. In recent reports, recombinant human growth hormone (rhGH) when administered systematically improved wound healing and whole body protein synthesis in severely burned patients and increased plasma pre-albumin and retinol-binding protein concentration in malnourished surgical patients. It is hypothesized that rhGH will increase the healing of chronic pressure ulcers inparaplegic patients. In order to test this hypothesis, the specific aims of this study are to: (1) evaluate the rate of wound closure caused by systematically administered rhGH as measured by changes in area and volume of the wound; (2) determine the rate of epithelialization of the wound caused by systemic administration of rhGH as measured by keratinocyte proliferation and migration; (3) determine the extent of upregulation of plasma IGF-I and IGF-1 binding proteins by systemic administration of rhGH; (4) quantify the effect of systematically administered rhGH on GH and IGF-I receptors in soft tissues of the wound involved as measured by GH and IGF-I binding studies, and (5) quantify the effect of systematically administered rhGH on IGF-I mRNA in soft tissues as the wound healing process occurs. The study sample will be 60 adult paraplegic patients with a Stage III/IV pressure ulcer meeting inclusion criteria for the study. The experimental group will receive subcutaneous injections of rhGH 0.2 mg/kg/day plus standard wound care for 35 days and the control will receive standard wound care. Data collection will include rate of wound closure, plasma levels of IGF-I and IGF-1 binding proteins, histological and molecular biological response to GH (IGF-I receptor and mRNA) in biopsy tissue. Descriptive statistics will be used to characterize demographic variables. Data will be analyzed using parametric and non-parametric statistics (t-Test or Mann-Whitney) to determine if the difference between the control and experimental group is statistically different at a level of P<.05. Findings from this study can add to the treatments available for chronic pressure ulcers, and will direct possible exploration of the additional vulnerary effects of IGF-1-BP administration, either systematically, or topically to avoid systemic glucose derangements that can occur.
