INHALED HUMAN INSULIN IN TYPE 2 DM ON SULFONYLUREA AND/OR METFORMIN

磺脲和/或二甲双胍吸入 2 型 DM 人胰岛素

• 批准号: 6415294
• 负责人: MARK N FEINGLOS
• 金额: $ 29.31万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-01 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6415294
• 关键词: clinical research; combination chemotherapy; diabetes mellitus therapy; drug screening /evaluation; human subject; human therapy evaluation; inhalation drug administration; insulin; metformin; noninsulin dependent diabetes mellitus; sulfonylurea

PURPOSE: The purpose of this study is to determine, in subjects with type 2 diabetes mellitus currently receiving a sulfonylurea and /or metformin as therapy (1) whether glycemic control can be improved, as measured by a decrease of at least 1% in the glycosylated hemoglobin, by the addition of a regimen of pre-meal inhaled insulin and (2) the toleration and safety of inhaled insulin therapy and its effects after 3 months, if any, on measures of pulmonary function. METHODS: In total, 60 subjects will participate in this trial, with approximately 6 being evaluated at this site. During this three-month comparative trial, half of the subjects will be randomized to receive an inhaled insulin regimen plus pre-study oral agent while the other half will continue pre-study oral agent. Patients who successfully complete this three-month trial will be eligible for a one-year, open-label protocol extension. Prior to study entry, subjects undergo a screening session, including a history and physical exam, EKG, CXR, and lab studies to verify that the patient is eligible for participation. This is followed by a 4 week baseline lead-in period, during which patients continue their pre-study oral agent. Subjects undergo pulmonary function tests (PFTs), dietary instruction, and home blood glucose monitoring instruction during this time. All patients are provided with a glucose meter and supplies and are required to perform blood glucose checks 4 times/day, to record doses and meter readings, and to document any hypoglycemic or adverse events which occur. At the end of the baseline period, subjects are admitted for a 2 day inpatient session, during which they are instructed in the use of the device and dosing with inhaled insulin. At the end of the admission, subjects are randomized to one of two treatment groups (premeal inhaled insulin plus oral hypoglycemic agent vs premeal inhaled placebo plus oral agent). Randomization is double-blinded and is stratified based on HbA1c. During the treatment period, patients are followed at weekly intervals. For the first 4 weeks of treatment, patients must return to the clinic for evaluation every week. After that, patients may return once every other week. Meal challenge studies will be performed at weeks 0,4,8, and 12, during which a patient will be asked to consume 16 oz of Sustacal beverage and timed blood draws measuring blood glucose and free insulin levels will be collected. Also at clinic visits, blood samples will be collected to evaluate HbA1c, fasting blood glucose, fructosamine, and lipids. Spirometry will be performed at week 6, and a full PFT battery will be repeated at week 12. In the optional one year extension, patients are required to return for monthly clinic visits. PFT's will be performed every 3 months. RESULTS AND CONCLUSIONS: The study is ongoing, and results are not available to date. SIGNIFICANCE: The Diabetes Control and Complications Trial (DCCT) demonstrated the long-term benefits of tight glycemic control. However, the clinical realization of the benefits of aggressive insulin therapy has been limited by the shortcomings of available SC delivery methods. In particular, multiple injection therapy has had poor patient acceptance. This study aims to determine whether the addition of a pre-meal inhaled insulin regimen can provide improved glycemic control to patients poorly controlled on oral agents. This system is designed to permit safe, non-invasive delivery of rapid-acting insulin in 1-2 inhalations per dose. If proven to be safe and effective, inhaled insulin, which is easy to administer and provides a predictable pattern of insulin action, may be more acceptable to patients requiring insulin therapy and may provide better overall glycemic control thereby possibly reducing the incidence of diabetic complications. Plans for phase III studies of inhaled insulin are currently underway by the study sponsor, Pfizer, Inc.

目得：本研究的目的是确定在目前接受磺脲类和/或二甲双胍治疗的2型糖尿病受试者中（1）血糖控制是否可以改善，如通过糖化血红蛋白降低至少1%所测量的，通过增加餐前吸入胰岛素的方案和（2）吸入胰岛素治疗的耐受性和安全性及其3个月后的效果，如果有的话，对肺功能的测量。方法：共有60例受试者将参加本试验，其中约6例在本中心接受评价。在这项为期三个月的比较试验中，一半受试者将随机接受吸入性胰岛素方案加研究前口服药物，而另一半将继续研究前口服药物。成功完成这项为期三个月的试验的患者将有资格获得为期一年的开放标签方案扩展。在进入研究之前，受试者接受筛选，包括病史和体格检查、EKG、CXR和实验室研究，以验证患者是否有资格参与研究。随后是4周的基线导入期，在此期间，患者继续其研究前口服药物。受试者在此期间接受肺功能测试（PFT）、饮食指导和家庭血糖监测指导。向所有患者提供血糖仪和用品，并要求每天进行4次血糖检查，记录剂量和血糖仪读数，并记录发生的任何低血糖或不良事件。在基线期结束时，受试者入院进行2天的住院治疗，在此期间，指导他们使用该装置和吸入胰岛素给药。在入院结束时，受试者被随机分配到两个治疗组之一（餐前吸入胰岛素加口服降糖药vs餐前吸入安慰剂加口服药物）。随机化是双盲的，并根据HbA 1c进行分层。在治疗期间，每周对患者进行随访。在治疗的前4周，患者必须每周返回诊所进行评估。之后，患者可以每隔一周返回一次。将在第0、4、8和12周进行膳食激发研究，在此期间，将要求患者饮用16盎司Sustacal饮料，并收集定时抽血测量血糖和游离胰岛素水平。同样在门诊访视时，将采集血液样本以评价HbA 1c、空腹血糖、果糖胺和血脂。将在第6周进行肺功能测定，并在第12周重复完整的PFT组合。在可选的一年延长期内，患者需要每月返回诊所就诊。PFT将每3个月进行一次。结果和结论：该研究正在进行中，迄今为止尚未获得结果。意义：糖尿病控制和并发症试验（DCCT）证明了严格血糖控制的长期益处。然而，积极胰岛素治疗的益处的临床实现受到可用SC递送方法的缺点的限制。特别地，多次注射疗法具有较差的患者接受性。本研究旨在确定是否增加餐前吸入胰岛素方案可以改善口服药物血糖控制不佳的患者的血糖控制。该系统设计用于安全、无创地输送速效胰岛素，每次吸入1-2次。如果证明是安全有效的，吸入胰岛素，这是易于管理和提供一个可预测的模式的胰岛素作用，可能更容易接受的患者需要胰岛素治疗，并可能提供更好的整体血糖控制，从而可能减少糖尿病并发症的发生率。研究申办者辉瑞公司目前正在进行吸入性胰岛素的III期研究计划。