An Intraperitoneal Insulin Delivery System for Management of Type 1 Diabetes

用于治疗 1 型糖尿病的腹膜内胰岛素输送系统

• 批准号: 10584462
• 负责人: Daniel Rogers Burnett
• 金额: $ 104.81万
• 依托单位: PERIKINETICS INC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10584462
• 关键词: Adoption; Advanced Development; Adverse event; Affect; Agitation; American; Animal Model; Animals; Attention; Body Temperature; Bolus Infusion; Brittle diabetes; Catheters; Characteristics; Chemicals; Clinical; Collaborations; Continuous Infusion; Custom; Devices; Disease; Drug Kinetics; Endocrine; Ensure; Esthetics; Europe; Evaluation; Excision; FDA approved; Family suidae; Feasibility Studies; Glucose; Goals; Health; High Pressure Liquid Chromatography; Histology; Hospitalization; Hour; Human; Hypoglycemia; Implant; Implantable venous access port; In Vitro; Infection; Infection prevention; Inflammation; Infusion procedures; Insulin; Insulin Infusion Systems; Insulin, Lispro, Human; Insulin-Dependent Diabetes Mellitus; Kinetics; Life; Liver; Location; Mechanics; Methods; Modeling; Modernization; Monitor; Needles; Obstruction; Operative Surgical Procedures; Patients; Pharmacodynamics; Phase; Physiological; Portal System; Positioning Attribute; Precipitation; Pump; Quality of life; Recombinants; Recurrence; Research; Risk; Safety; Small Business Innovation Research Grant; System; Testing; Time; Tissues; Visual; absorption; analog; biomaterial compatibility; blood glucose regulation; commercialization; cytotoxicity; delivery vehicle; design; diabetic; diabetic patient; experimental study; glycemic control; implantation; improved; in vivo; infection rate; innovation; intraperitoneal; intraperitoneal infusion; irritation; nephelometry; preclinical development; preclinical safety; research study; response; satisfaction; seal; stability testing; subcutaneous; systemic toxicity

ABSTRACT Perikinetics’ intraperitoneal (IP) insulin delivery system for the management of Type 1 diabetes (T1D) utilizes an innovative implantable port-catheter system accessed by a proprietary external infusion set to provide a safe and effective means of tight glycemic control. For the 1.6 million Americans living with T1D, modern technological advances have improved glucose sensing and insulin delivery, however, achieving tight glycemic control remains challenging. The IP cavity presents a superior location for insulin delivery for T1D patients. IP insulin delivery better mimics physiological delivery by providing a higher insulin concentration in the portal system, enabling rapid absorption by the liver, and a more effective response to glycemic disturbances and reduced hypoglycemic episodes. Continuous IP insulin infusion (CIPII) systems developed to date have demonstrated dramatic improvement in glucose regulation but, unfortunately, suffer from catheter obstruction, infection, and aesthetic disfigurement. No FDA approved CIPII systems are currently available in the U.S. Improving the safety and clinical utility of IP insulin devices would enable commercialization of a superior option for glycemic control within a tighter monitoring range. Perikinetics (PK) has developed the PK Insulin Delivery Conduit (IDC), an implantable port-catheter system accessed by a proprietary external infusion set for IP insulin delivery. In our Phase I equivalent research studies, we established feasibility of the system through in vitro flow characterization, implant viability, and mechanical integrity testing. The overall objective of this proposal is to demonstrate that the PK IDC can safely and effectively deliver basal and bolus insulin in a T1D animal model. In Specific Aim 1, we will assess insulin stability on the bench to ensure that injected insulin will not be adversely affected by the device or delivery method. In Specific Aim 2, we will conduct a pilot animal study to validate safety, efficacy, and clinical utility of the PK IDC. Successful completion of these aims will position the device for IDE-enabling studies and, ultimately, de novo 510(k) clearance as the first IP insulin delivery vehicle using a subcutaneous port to reduce infection and improve quality of life.

摘要 Periketics用于治疗1型糖尿病（T1 D）的腹膜内（IP）胰岛素输送系统利用 创新的植入式输液港-导管系统，通过专有的外部输液器进行接入， 和严格血糖控制的有效手段。对于160万患有T1 D的美国人来说， 尽管这些进展已经改善了葡萄糖传感和胰岛素输送，但是，实现严格的血糖控制仍然是一个挑战。 挑战性IP腔为T1 D患者提供了胰岛素输注的上级位置。IP胰岛素输注 通过在门静脉系统中提供更高的胰岛素浓度， 肝脏快速吸收，对血糖紊乱和低血糖反应更有效 情节。迄今为止开发的连续IP胰岛素输注（CIPII）系统已经显示出显著的 但不幸是，存在导管阻塞、感染和美观问题 毁容目前在美国没有FDA批准的CIPII系统。 IP胰岛素装置的临床实用性将使得用于血糖控制的上级选择能够商业化 更严密的监控范围。Perikinetics（PK）开发了PK胰岛素输送导管（IDC）， 输液港-导管系统，通过专有外部输注管路进行IP胰岛素输注。在我们的第一阶段 等效研究，我们通过体外流动表征、植入 活力和机械完整性测试。本提案的总体目标是证明PK IDC可以在T1 D动物模型中安全有效地输送基础胰岛素和餐时胰岛素。具体目标1： 在工作台上评估胰岛素稳定性，以确保注射的胰岛素不会受到器械的不良影响 或交付方式。在具体目标2中，我们将进行一项初步动物研究，以验证安全性、有效性和临床意义。 PK IDC的应用。这些目标的成功完成将使该器械能够用于IDE使能研究， 最终，重新获得510（k）许可，成为第一个使用皮下输液港的IP胰岛素输送载体，以减少 感染和改善生活质量。