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.

这项研究是一项随机，双盲，安慰剂对照的跨界试验，比较了吡格列酮与安慰剂在26名严重，难治性哮喘的受试者中的作用。 这项研究的目的是评估吡格列酮盐酸盐对严重，难治性哮喘患者的功效。 主要目的是评估氢化盐酸苯酮是否可以改善生活质量。 次要目标是评估苯丙酮盐酸盐对气道炎症，气流阻塞，气道高反应性和哮喘症状指标的功效。 我们将最多筛选300名受试者，以获得26个完成的研究。 研究参与者必须年龄在18至75岁之间，并且可以是男性或女性。 将向患者提供有关替代治疗选择的建议。 将筛选患者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，BMI，恶化病史和OTC化合物的使用草药/补充剂），呼吸测试（肺功能测试），胸部X射线，心电图（心脏故），心脏心动图（心脏践踏），超声心动图（使用声波来测试心脏测试的声音），血液测试，并怀孕。 受试者将根据以下因素归类为患有哮喘。 首先，他们一定偶尔会喘息。 其次，我们将证明它们具有异常的肺功能，并且在过去的某个时刻曾具有气道高反应性。 他们将被要求在呼吸一种称为Albuterol的药物之前和之后进行呼吸测试，如果患有哮喘，应放松其肺管。 Albuterol用于治疗哮喘，应改善它们可以呼吸的气体量。 它们必须在白化醇治疗后的肺功能有显着改善，或者在研究中的某个时刻对甲基苯胺测试的异常反应。 Albuterol吸入是一种常规测试，用于评估肺部疾病患者。 符合纳入和排除标准的受试者将被邀请参加研究。 该研究将分为5个时间段；一个为期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），分别是8周的冲洗（第3阶段），其中包括在周期中进行的第二个4周（3A阶段）和4周的随访期（第5阶段），进行48周的总研究持续时间为48周。 我们预计将需要2次门诊就诊来完成筛查评估。 因此，该研究将包括14个门诊就诊。 I阶段和III阶段：在随机接受吡格列酮或安慰剂之前，患者将参与为期4周的磨合期，在此期间将记录基线症状。 受试者必须在磨合期内患有稳定的哮喘，这将定义为：缺乏针对哮喘护理的外科医疗保健访问，并且哮喘维持药物没有变化。 研究对象还必须遵守对哮喘症状的家庭监测和在磨合期间的峰值呼气流量，以便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量的研究受试者不会随机地接受吡格列酮或安慰剂。 除了在治疗期间所述的测试（第2阶段和第4阶段）之外，仅在第一个磨合期（第0周）完成时，还将进行过敏的皮肤测试和甲基甲胆碱支气管胆汁固醇测试。 研究员将出席用于气降盐皮肤测试和甲氧甲促甲胆碱应测试。 II和IV期治疗阶段：受试者将由NIH临床中心药房随机分组，以接收吡格列酮或安慰剂，该安慰剂将与主动治疗相匹配。 每个治疗阶段的前2周，受试者每天将接受30毫克的pioglitazone，然后每天升级为45毫克的吡格列酮或安慰剂，或安慰剂3周至第16周。 受试者将每月每月监视门诊病人，为期第0-16周（+/- 10天）和24 40周（+/- 10天）。 每次访问中要进行的研究将包括：历史和体格检查（包括发病年龄，BMI，加剧历史）； 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他们的初级保健医师将收到通知）；肺活量测定法（支气管扩张剂前后）注意：将在每个治疗期的开始和结束（第0、16、24、40周的开始和结尾）执行全PFT（带有前/后BD）；体重和体重指数；哮喘控制评分；哮喘的生活质量评分；测量呼出的一氧化氮；和妊娠试验。 受试者将使他们的哮喘症状评分，吸入B-激动剂的使用，夜间觉醒以及需要进行哮喘症状外医疗护理的需求（紧急医师或急诊科，住院，住院）。 每天的早晨和晚上的PEF和FEV1将通过电子记录。 研究参与者将提供一个电子峰值流量计，以用于PEF和FEV1的家庭监视。 第三阶段的冲洗期：在此期间，将不服用研究药物。 在第20周（第二阶段）（第3A阶段）的开始时，评估将与治疗期间的评估和测试相同。 第五阶段的随访评估期：受试者将在第二阶段治疗阶段完成后4周进行对II和IV阶段所述的测试，除了妊娠试验和研究血液（第44周）。 这项研究得到了NHLBI IRB于07年12月18日批准，到目前为止，已经招募了29名受试者，迄今为止，已完成了4名受试者。