TRIAL TO ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS OF GLUCAGON IN TYPE I

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The first proof of principle pilot study entitled :A Phase 1, Multicenter, Open Label, Clinical Trial to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Very Low Dose Glucagon (VLD Glucagon) in Subjects with Type 1 Diabetes Mellitus" will validate the prophylactic use of VLD glucagon in Type 1 diabetes to prevent or blunt insulin-induced hypoglycemia. The objectives of the study are to evaluate the pharmacokinetics and pharmacodynamics and the safety and tolerability of VLD glucagon administered as a continuous subcutaneous infusion in subjects with type 1 diabetes mellitus treated with continous subcutaneous infusion of insulin (CSII) The study will enroll up to 25 subjects, who have type 1 deabetes mellitus for > 10 years and who are well controlled on a stable regimen of CSII therapy. Each eligible subject will have a series of 5 GCRC visits, each consisting of 1-day (overnight) admission. A study evaluation period will be terminated immediately in the event of blood glucose less than or equal to 50mg/dL or greater than or equal to 250 mg.dL. After overnight fasting and while on their usual basal insulin infusion each subject will receive an infusion of either vehicle or VDL glucagon based on a protocol specific algorihm via a second subcutaneous pump from 7 AM until 1 PM. Glycemic control to the study drug will be monitored by frequent blood glucose (every 5-15 min). Visits 1-3 will determine the concentration of glucagon that doesn't cause hyperglycemia. In study visits 4 and 5, the subject usual basal infusion rate of insulin will be doubled to induce hypoglycemia. At visit 4, the second pump will infuse vehicle and at visit 5 the concentration of VLD glucagon will be infused that did not cause hyperglycemia in visits 2 or 3. The objective of the study visit 5 is to blunt or prevent insulin induced hypoglycemia without causing hyperglycemia.