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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。第一个原理证明试点研究题为：1型糖尿病患者使用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1期、多中心、开放标签临床试验，将验证在1型糖尿病患者中预防性使用VLD胰高血糖素以预防或减轻胰岛素诱导的低血糖。该研究的目的是评估持续皮下输注VLD胰高血糖素对持续皮下输注胰岛素（CSII）治疗的1型糖尿病患者的药代动力学和药效学以及安全性和耐受性。该研究将招募多达25名患者，他们患有1型糖尿病，并在持续皮下输注胰岛素（CSII）治疗方案中得到良好控制。每位符合条件的受试者将有5次GCRC访问，每次访问包括1天（过夜）的入院时间。当血糖低于或等于50mg/dL或大于或等于250mg /dL时，研究评估期将立即终止。禁食过夜后，在常规基础胰岛素输注的同时，每个受试者将根据特定的方案算法，从早上7点到下午1点通过第二个皮下泵输注车辆或VDL胰高血糖素。通过频繁的血糖监测（每5-15分钟）来监测对研究药物的血糖控制。第1-3次检查将确定不会引起高血糖的胰高血糖素浓度。在研究访视4和5中，受试者通常的基础胰岛素输注速率将增加一倍以诱导低血糖。在第4次就诊时，第二个泵将输注车辆，在第5次就诊时，将输注在第2次或第3次就诊时没有引起高血糖的VLD胰高血糖素浓度。研究访问5的目的是在不引起高血糖的情况下钝化或预防胰岛素诱导的低血糖。

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.