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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。第一项题为“一项在1型糖尿病受试者中评估极低剂量胰高血糖素（VLD胰高血糖素）的安全性、耐受性、药代动力学和药效学的I期、多中心、开放标签临床试验”的原则性初步研究将验证VLD胰高血糖素在1型糖尿病中的预防性使用，以预防或减轻胰岛素诱导的低血糖症。本研究的目的是在接受胰岛素连续皮下输注（CSII）治疗的1型糖尿病受试者中评价VLD胰高血糖素连续皮下输注给药的药代动力学和药效学以及安全性和耐受性。本研究将招募多达25名受试者，患有1型糖尿病> 10年，并且在稳定的CSII治疗方案下控制良好。每例合格受试者将接受5次GCRC访视，每次包括1天（过夜）住院。如果血糖小于或等于50 mg/dL或大于或等于250 mg. dL，则立即终止研究评价期。禁食过夜后，在进行常规基础胰岛素输注时，每例受试者将根据方案特定算法，从上午7点至下午1点通过第二个皮下泵接受溶媒或VDL胰高血糖素输注。将通过频繁血糖（每5-15分钟一次）监测研究药物的血糖控制。访视1-3将确定不会引起高血糖症的胰高血糖素浓度。在研究访视4和5中，受试者的胰岛素常规基础输注速率将加倍，以诱导低血糖。在访视4时，第二个泵将输注溶剂，在访视5时，将输注访视2或3时未引起高血糖症的VLD胰高血糖素浓度。研究访视5的目的是减弱或预防胰岛素诱导的低血糖，而不引起高血糖。

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.