Dose-Response Study of Human Growth Hormone in Venous Ulcers: Influence on Healing and Synthesis of Collagen Types I and III

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Abstract
Objective: To investigate the dose-response effect of topical human growth hormone on healing and local collagen synthesis and to study procollagen propeptides as markers of healing in chronic venous ulcers. Design: Double-blind, placebo-controlled study. Setting: Multicentre study, University Hospitals of Copenhagen, Denmark. Patients: Eighty-seven patients with chronic venous ulcers. Interventions: Solutions of growth hormone (Norditropin), 0.17 IU/ml, 1 IU/ml and 11.2 IU/ml, 0.1 ml/cm2/day, or placebo (groups 1–4) was administered daily except weekends for 6 weeks. Main outcome measures: Healing rates evaluated as weekly ulcer area reduction and complete healing. Local collagen synthesis was evaluated by measurement of the propeptides of collagen types I and III (PICP and PIIINP) in wound washings twice weekly during the first 3 weeks. Results: No significant difference in ulcer area reduction between the groups was seen, although patients treated with 0.17 IU/ml healed faster than the other groups ( p = 0.14). Nine (45%), five (29%), seven (31%) and six (31%) ulcers in groups 1–4 respectively were healed at follow-up ( p = 0.06–0.1, log rank test). PICP and PIINP increased by 21.4% per week, (14.5–28% per week) and 20.2% per week, (12.2–28.2% per week) respectively compared with placebo, p < 0.05. Both PIIINP and PICP at 3 weeks correlated significantly with the healing rates, r = 0.44, p < 0.001 and r = 0.34, p < 0.005. Conclusion: The study failed to demonstrate a significant influence on healing, whereas collagen synthesis was stimulated dose-dependently by growth hormone. Procollagen propeptides are sensitive markers of growth hormone action and may be useful markers of healing in clinical investigations in chronic venous ulcers. Lower doses of growth hormone should be considered in future studies.