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

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。第一项原则证明先导研究题为：评估极低剂量胰高血糖素在1型糖尿病患者中的安全性、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极低剂量胰高血糖素预防或抑制胰岛素诱导的低血糖。这项研究的目的是评估VLD高血糖素作为持续皮下注射胰岛素(CSII)治疗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。这项研究将纳入25名1型糖尿病患者，他们患有1型糖尿病10年，并在CSII治疗的稳定方案下得到良好控制。每名合资格的受试者将有一系列的五次GCRC访问，每次包括一天(隔夜)入场。如果血糖低于或等于50毫克/分升或大于或等于250毫克/分升，研究评估期将立即终止。在隔夜禁食后，在通常的基础胰岛素输注下，每个受试者将从上午7点至下午1点通过第二次皮下泵接受基于特定方案的算法的载体或VDL高血糖素输注对研究药物的血糖控制将通过频繁的血糖监测(每隔5-15分钟)。检查1-3将确定不会导致高血糖的胰高血糖素浓度。在第4次和第5次研究中，受试者通常的基础胰岛素输注率将增加一倍，以诱导低血糖。在访视4，第二泵将输注载体，在访视5，VLD胰高血糖素浓度将被输注在访视2或3未引起高血糖。研究访视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.