Study of Pioglitazone Hydrochloride in Severe, Refractory Asthma

盐酸吡格列酮治疗严重难治性哮喘的研究

• 批准号: 8344773
• 负责人: Stewart Levine
• 金额: $ 42.6万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8344773
• 关键词: Accident and Emergency department; Age; Age of Onset; Agonist; Albuterol; Alkaline Phosphatase; Allergens; Asthma; Bilirubin; Blood; Blood Tests; Body mass index; Breathing; Bronchodilator Agents; Calcifediol; Caring; Chest; Clinical; Counseling; Creatinine; Cross-Over Studies; Double-Blind Method; Echocardiography; Electrocardiogram; Electrolytes; Electronics; Enrollment; Evaluation; Exclusion Criteria; Exhalation; Extrinsic asthma; Female; Gases; Genetic Crossing Over; Health Care Visit; Heart; Heart Function Tests; Herb; Home environment; Hospitalization; Hydrochloride Salt; Hypersensitivity; Hypersensitivity skin testing; IgE; Institutional Review Boards; Life; Lung; Lung diseases; Maintenance; Measurement; Mediating; Medical; Modeling; Monitor; Mus; National Heart, Lung, and Blood Institute; Nitric Oxide; Obstruction; Outpatients; PPAR gamma; Participant; Patients; Peak Expiratory Flow; Peak Expiratory Flow Rate; Pharmaceutical Preparations; Pharmacy facility; Phase; Physical Examination; Physicians; Pilot Projects; Pioglitazone; Placebo Control; Placebos; Pregnancy Tests; Primary Care Physician; Protocols documentation; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary function tests; Quality of life; Questionnaires; Randomized; Recording of previous events; Refractory; Research; Research Personnel; Respiratory physiology; Running; Screening procedure; Spirometry; Study Subject; Symptoms; Takeda brand of pioglitazone hydrochloride; Testing; Time; Transaminases; Tube; United States National Institutes of Health; Visit; Vitamin D; Weight; Wheezing; active method; airborne allergen; airway hyperresponsiveness; airway inflammation; alternative treatment; base; eosinophil; evaluation/testing; follow-up; improved; inclusion criteria; indexing; male; meetings; meter; methacholine; neutrophil; response; sound; standard measure; treatment duration; trial comparing

This study is a randomized, double-blind, placebo-controlled, crossover trial comparing the effects of pioglitazone versus placebo in 26 subjects with severe, refractory asthma. The objective of this study will be to assess the efficacy of pioglitazone hydrochloride for patients with severe, refractory asthma. The primary objective is to assess whether pioglitazone hydrochloride can improve quality of life. The secondary objectives are to assess the efficacy of pioglitazone hydrochloride on indices of airway inflammation, airflow obstruction, airway hyperreactivity, and asthma symptoms. We will screen up to 300 subjects to obtain 26 completed studies. Study participants must be between the ages of 18 and 75 and can be male or female. Patients will be counseled regarding alternative treatment options. Patients will be screened to assess whether they meet the inclusion and exclusion criteria. The following studies will be performed: history and physical examination (including age of onset, BMI, exacerbation history and use of OTC compounds herbs/supplements), breathing tests (pulmonary function tests), chest x-ray, electrocardiogram (heart tracing), echocardiogram (uses sound waves to test the function of the heart), blood tests, and pregnancy test. Subjects will be classified as having asthma on the basis of the following factors. First, they must have had occasional wheezing. Second, we will show that they have abnormal lung function and have had airway hyperreactivity at some point in their past. They will be asked to perform breathing tests before and after they breathe a medication called albuterol, which should relax their lung tubes if they have asthma. Albuterol is used to treat asthma and should improve the amount of gas they can breathe out. They must have either a significant improvement in lung function following an albuterol treatment, or an abnormal response to methacholine testing, at some point in their life, to be included in the study. Albuterol inhalation is a routine test that is used to evaluate patients with lung disease. Subjects who fulfill the inclusion and exclusion criteria will be invited to participate in the study. The study will be divided into 5 time periods; a 4-week run-in period (Phase 1), two 16-week treatment periods (Phases 2 and 4) separated by an 8 week washout (Phase 3), which includes a second 4 week run in period (Phase 3a), and a 4-week follow-up period (Phase 5), for a total study duration of 48 weeks. We anticipate 2 outpatient visits will be required to complete the screening assessment. Therefore, the study will include 14 outpatient visits. Phase I and III Run-in Phase: Prior to being randomized to receive pioglitazone or placebo, patients will participate in a 4-week run-in phase, during which time baseline symptoms will be documented. Subjects must have stable asthma during the run-in period, which will be defined as: absence of unscheduled health care visit for asthma care and no change in asthma maintenance medications. Study subjects must also comply with home monitoring of asthma symptoms and peak expiratory flow during the run-in period to be eligible to proceed to the treatment phase. Study subjects who are unable to monitor daily asthma symptoms and peak expiratory flow rates will not be randomized to receive pioglitazone or placebo. Only at the completion of the first run-in period (week 0), in addition to the testing described for the Treatment Periods (Phases 2 and 4), allergy skin testing and methacholine bronchoprovocation testing will be performed. An investigator will be present for aeroallergen skin testing and methacholine bronchoprovocation testing. Phase II and IV - Treatment Phase: Subjects will be randomized by the NIH Clinical Center pharmacy to receive either pioglitazone or a placebo that will match the active treatment. Subjects will receive 30 mg daily ofpioglitazone for the first 2 weeks of each treatment phase and then be escalated to 45 mg daily of pioglitazone or placebo for weeks 3 through 16. Subjects will be monitored as outpatients on a monthly basis for weeks 0 - 16 (+/- 10 days) and weeks 24 40 (+/- 10 days). Studies to be performed at each visit will include: history and physical examination (including age of onset, BMI, exacerbation history); blood draw (CBC including differential including absolute and percentage eosinophils and neutrophils, electrolytes including BUN, creatinine, LFTs including transaminases, bilirubin, alkaline phosphatase, IgE, CPK, pro-BNP, research weeks 0, 16, 24, 40, and Vitamin D, 25-hydroxycholecalciferol level Week 0; if abnormal, the subject and their primary care physician will be notified); spirometry (pre- and post-bronchodilator) Note: Full PFTs (with pre/post BD) will be performed in place of spirometry at the beginning and end of each of the Treatment Periods (Weeks 0, 16, 24, 40); weight and body mass index; asthma control score; Asthma Quality of Life Score; measurement of exhaled nitric oxide; and pregnancy test. Subjects will keep a log at home of their asthma symptom score, inhaled b-agonist use, nocturnal awakenings and need for unscheduled medical care for asthma symptoms (urgent physician or emergency department visit, hospitalization). The daily morning and evening PEF and FEV1 will be recorded electronically. Study participants will be provided with an electronic peak flow meter for home monitoring of PEF and FEV1.. Phase III Wash-out Period: During this period, no study medications will be administered. At week 20, the beginning of the second Run-In Period (Phase 3a), evaluation will be the same as the evaluation and testing during the treatment periods. Phase V Follow-up Evaluation Period: Subjects will undergo a follow-up evaluation, with testing as described for phases II and IV, at 4 weeks after the completion of the 2nd treatment phase, with the exception of pregnancy test and research blood (week 44). This study was approved by the NHLBI IRB on 12/18/07 and there have been 29 subjects enrolled thus far and four subjects have completed the study to date.

本研究是一项随机、双盲、安慰剂对照、交叉试验，比较了吡格列酮与安慰剂在 26 名患有严重难治性哮喘受试者中的效果。 本研究的目的是评估盐酸吡格列酮对严重难治性哮喘患者的疗效。 主要目的是评估盐酸吡格列酮是否可以改善生活质量。 次要目标是评估盐酸吡格列酮对气道炎症、气流阻塞、气道高反应性和哮喘症状指标的功效。 我们将筛选多达 300 名受试者以获得 26 项已完成的研究。 研究参与者的年龄必须在 18 岁至 75 岁之间，并且可以是男性或女性。 将就替代治疗方案向患者提供建议。 将对患者进行筛查，以评估他们是否符合纳入和排除标准。 将进行以下研究：病史和体格检查（包括发病年龄、体重指数、恶化史和非处方药复合草药/补充剂的使用）、呼吸测试（肺功能测试）、胸部X光检查、心电图（心脏描记）、超声心动图（使用声波测试心脏功能）、血液测试和妊娠测试。 将根据以下因素将受试者分类为患有哮喘。 首先，他们肯定偶尔有喘息的情况。 其次，我们将证明他们的肺功能异常，并且在过去的某个时候曾出现过气道高反应性。 他们将被要求在吸入一种名为沙丁胺醇的药物之前和之后进行呼吸测试，如果他们患有哮喘，这种药物可以放松他们的肺管。 沙丁胺醇用于治疗哮喘，应该可以增加呼出的气体量。 他们必须在沙丁胺醇治疗后肺功能显着改善，或者在生命中的某个时刻对乙酰甲胆碱测试有异常反应，才能被纳入研究。 沙丁胺醇吸入是一项常规测试，用于评估患有肺部疾病的患者。 符合纳入和排除标准的受试者将被邀请参加该研究。 研究将分为5个时间段； 4 周的磨合期（第 1 阶段）、两个 16 周的治疗期（第 2 阶段和第 4 阶段）以及 8 周的冲洗期（第 3 阶段），其中包括第二个 4 周的磨合期（第 3a 阶段），以及 4 周的随访期（第 5 阶段），总研究持续时间为 48 周。 我们预计需要两次门诊才能完成筛查评估。 因此，该研究将包括 14 次门诊就诊。 I 期和 III 期磨合期：在随机接受吡格列酮或安慰剂治疗之前，患者将参加为期 4 周的磨合期，在此期间将记录基线症状。 受试者在磨合期内必须患有稳定的哮喘，这将被定义为：没有因哮喘护理而进行计划外的医疗保健访问并且没有改变哮喘维持药物。 研究对象还必须遵守磨合期哮喘症状和呼气峰流量的家庭监测，才有资格进入治疗阶段。 无法监测每日哮喘症状和峰值呼气流速的研究受试者将不会被随机分配接受吡格列酮或安慰剂治疗。 仅在第一个磨合期（第 0 周）完成时，除了治疗期（第 2 阶段和第 4 阶段）所述的测试之外，还将进行皮肤过敏测试和乙酰甲胆碱支气管激发测试。 一名调查员将在场进行空气过敏原皮肤测试和乙酰甲胆碱支气管激发测试。 II 期和 IV 期 - 治疗阶段：NIH 临床中心药房将随机分配受试者接受匹格列酮或与活性治疗相匹配的安慰剂。 受试者将在每个治疗阶段的前 2 周每天接受 30 毫克吡格列酮，然后在第 3 周至第 16 周逐步增加至每天 45 毫克吡格列酮或安慰剂。 将在第 0 - 16 周（+/- 10 天）和第 24 至 40 周（+/- 10 天）每月对受试者进行门诊监测。 每次就诊时进行的研究将包括： 病史和体格检查（包括发病年龄、体重指数、恶化史）；抽血（CBC，包括嗜酸性粒细胞和中性粒细胞绝对值和百分比、电解质（包括 BUN、肌酐）、LFT（包括转氨酶、胆红素、碱性磷酸酶、IgE、CPK、pro-BNP、研究第 0、16、24、40 周和维生素 D、第 0 周 25-羟基胆钙化醇水平；如果异常，受试者 并且将通知他们的初级保健医生）；肺活量测定（支气管扩张剂前和后） 注意：将在每个治疗期（第 0、16、24、40 周）开始和结束时进行全面 PFT（使用 BD 前/后）代替肺活量测定；体重和体重指数；哮喘控制评分；哮喘生活质量评分；呼出一氧化氮的测量；和妊娠测试。 受试者将在家中记录其哮喘症状评分、吸入β受体激动剂的使用、夜间觉醒以及针对哮喘症状需要的计划外医疗护理（紧急医生或急诊科就诊、住院治疗）。 每天早上和晚上的 PEF 和 FEV1 将以电子方式记录。 研究参与者将获得一个电子峰值流量计，用于家庭监测 PEF 和 FEV1。 第三阶段清除期：在此期间，不会给予研究药物。 在第 20 周，即第二个磨合期（第 3a 阶段）开始时，评估将与治疗期间的评估和测试相同。 V 期随访评估期：受试者将在第二个治疗阶段完成后 4 周接受后续评估，并进行 II 期和 IV 期所述的测试，妊娠测试和研究血液（第 44 周）除外。 这项研究于 2007 年 12 月 18 日获得 NHLBI IRB 批准，迄今为止已有 29 名受试者入组，其中 4 名受试者已完成研究。