Clinical studies of a bionic pancreas for automated glucose management in cystic fibrosis-related diabetes mellitus

仿生胰腺用于囊性纤维化相关糖尿病自动血糖管理的临床研究

• 批准号: 10352204
• 负责人: Melissa Susan Putman
• 金额: $ 60.4万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-16 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10352204
• 关键词: Acute; Address; Adherence; Adolescent; Adult; Affect; Artificial Pancreas; Automation; Bionics; Blood Glucose; Body Composition; Body Weight decreased; Body mass index; Boston; Calories; Carbohydrates; Caring; Caucasians; Cessation of life; Clinical; Clinical Research; Collaborations; Consumption; Coupled; Cross-Over Trials; Crossover Design; Cystic Fibrosis; Dangerousness; Deterioration; Development; Devices; Diabetes Mellitus; Diet; Disease; Dose; European; Exocrine pancreatic insufficiency; Fibrosis; Formulation; Glucagon; Glucocorticoids; Glucose; Goals; Hormonal; Hospitalization; Hour; Hyperglycemia; Hypoglycemia; Infection; Injections; Inpatients; Insulin; Insulin Infusion Systems; Insulin-Dependent Diabetes Mellitus; Intake; Lead; Life; Live Birth; Lung; Lung diseases; Medical; Monitor; Morbidity - disease rate; Nutritional status; Outcome; Outpatients; Pancreas; Patients; Performance; Persons; Population; Prevention; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary Inflammation; Pump; Quality of life; Questionnaires; Randomized; Regulation; Risk; Safety; Suspensions; System; Technology; Testing; Time; United States; Universities; Weight; Weight Gain; Work; base; care burden; cystic fibrosis patients; cystic fibrosis related diabetes; design; diabetes management; experience; feasibility trial; glucose monitor; glycemic control; high risk; improved; inpatient service; mathematical algorithm; mortality; nutrition; patient population; premature; prevent; primary outcome; pulmonary function; satisfaction; sensor; treatment as usual; trial comparing; trial design

Project Summary Cystic fibrosis (CF) is the most common autosomal recessive disease affecting Caucasian populations and causes progressive pulmonary decline and multi-organ disease leading to premature death. Cystic fibrosis- related diabetes (CFRD) affects up to half of adults with CF. Development of CFRD is associated with clinical deterioration including decline in pulmonary function, compromised nutritional status, and increased mortality. Insulin is the only recommended treatment for CFRD and has been demonstrated to improve clinical status and decrease mortality. Patients with CF already carry a significant medical burden managing the pulmonary manifestations of their disease, and the additional onus of frequent blood sugar monitoring and insulin injections that accompanies CFRD often leads to a decline in quality of life and non-adherence. One of the most promising strategies to improve glycemic regulation in people with type 1 diabetes (T1D) is automation of glycemic regulation with artificial pancreas (AP) devices. We have tested an AP device called the bionic pancreas extensively in subjects with T1D and have shown that it simultaneously reduces both mean glucose and hypoglycemia while reducing the work required for diabetes management and improving quality of life. There are several unique features of the bionic pancreas that make it ideally suited among AP systems for use in the CFRD population. The bionic pancreas rapidly and automatically adapts to a wide range of insulin needs, making it well suited to address fluctuations in insulin requirements of those with CFRD that occur during acute CF exacerbations and treatment with glucocorticoids. In addition, it is not necessary to carbohydrate count or inform the bionic pancreas when a meal is going to be eaten to achieve good glycemic control, which will be particularly useful for patients with CF who require frequent high calorie, high carbohydrate meals and snacks to maintain an adequate nutritional status. Moreover, the bihormonal configuration of the bionic pancreas, which can use micro-dose glucagon to prevent hypoglycemia when suspension of insulin delivery is insufficient, may be particularly useful for prevention of hypoglycemia in patients with CFRD, who are already at high risk for hypoglycemia due to pancreatic fibrosis leading to glucagon deficiency. In this proposal we will test the ability of the bionic pancreas to control blood glucose levels in subjects with CFRD with the following three aims: (1) We will test the short-term safety and efficacy of two configurations of the bionic pancreas, bihormonal (insulin/glucagon) and insulin-only, versus usual care in subjects with CFRD; (2) we will compare the long-term outpatient performance of the bionic pancreas versus usual care over a period of 6 months and look for preliminary evidence of improvement in non-glycemic outcomes such as pulmonary function, weight, and number of CF exacerbations; and (3) we will compare the bionic pancreas to usual glycemic inpatient management in patients with CFRD during hospitalizations for CF exacerbations, which are often associated with difficulty in glycemic management.

项目摘要 囊性纤维化（CF）是影响高加索人群的最常见的常染色体隐性遗传疾病， 导致进行性肺功能下降和多器官疾病，导致过早死亡。囊性纤维化- 相关糖尿病（CFRD）影响多达一半的CF成人。面板堆石坝的发展与临床 恶化，包括肺功能下降、营养状况受损和死亡率增加。 胰岛素是CFRD唯一推荐的治疗方法，已被证明可改善临床状态 降低死亡率。患有CF的患者已经承担了管理肺部疾病的重大医疗负担。 他们的疾病表现，以及频繁血糖监测和胰岛素的额外负担 伴随CFRD的注射通常导致生活质量下降和不依从。之一 改善1型糖尿病（T1 D）患者血糖调节的最有前途的策略是自动化 使用人工胰腺（AP）装置进行血糖调节。我们测试了一种叫做仿生的AP设备 在T1 D受试者中广泛存在于胰腺中，并已显示其同时降低了平均葡萄糖 和低血糖，同时减少糖尿病管理所需的工作并提高生活质量。 仿生胰腺有几个独特的功能，使其非常适合在AP系统中使用 在CFRD人群中。仿生胰腺快速自动适应各种胰岛素 需要，使其非常适合于解决那些与CFRD发生胰岛素需求的波动， 在急性CF恶化和糖皮质激素治疗期间。此外，没有必要 碳水化合物计数或通知仿生胰腺，当一顿饭要吃，以实现良好的血糖 控制，这将是特别有用的CF患者谁需要频繁的高热量，高 碳水化合物餐和零食，以保持足够的营养状况。此外，双激素 仿生胰腺的配置，它可以使用微剂量胰高血糖素，以防止低血糖， 暂停胰岛素输送是不够的，对于预防低血糖症可能特别有用， CFRD患者，由于胰腺纤维化已经处于低血糖的高风险中， 胰高血糖素缺乏在这个提议中我们将测试仿生胰腺控制血糖的能力 本研究的目的有三：（1）我们将检测 仿生胰腺的两种配置，双激素（胰岛素/胰高血糖素）和仅胰岛素，与常规护理相比， （2）我们将比较仿生胰腺与 在6个月的时间内进行常规护理，并寻找非血糖改善的初步证据 结果，如肺功能、体重和CF恶化次数;（3）我们将比较 CFRD患者因CF住院期间仿生胰腺与常规血糖住院管理的比较 急性加重，通常与血糖管理困难相关。