A Randomized, Double-Blinded, Placebo-Controlled Protocol of Oral Cyclosporine in Patients With Advanced Stage Chronic Obstructive Pulmonary Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients - Number of Patients That Developed Infection Requiring Systemic Antibiotic Therapy
研究概览
简要总结
This is a randomized, double-blinded, placebo-controlled trial of oral Cyclosporine A (CsA) in patients with advanced stage chronic obstructive pulmonary disease. The purpose of the study is to evaluate the safety and effectiveness of CsA as a therapy for the adaptive immune response in advanced stage Chronic Obstructive Pulmonary Disease (COPD).
Subjects between 45 and 80 years of age with a confirmed diagnosis of advanced stage COPD, not responsive to conventional inhaler therapy, who meet all the study requirements, will be enrolled in this study. A total of 30 subjects of either sex will be enrolled in this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 45 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 45 and 80 years
- •A confirmed diagnosis of advanced stage COPD, using current accepted diagnostic criteria, including clinical/laboratory findings, pulmonary function tests, and appropriate history to exclude other disorders that could explain their lung disease. The accepted range of forced expiratory volume at one second will include 25% ≤ forced expiratory volume at one second ≤ 60%
- •Subjects agree to maintain a stable medication regimen in the absence of a disease flare
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- •carbon dioxide partial pressure < 45 mm Hg, room air oxyhemoglobin saturation > 85%
- •A willingness to participate in all portions of the protocol, including serial bronchoscopy, requisite surveillances, and ancillary immunologic studies in follow-up visits at this institution
- •For woman of childbearing age, a negative pregnancy test, and a willingness to use two methods of contraception, or abstinence
- •An ability and willingness to provide written informed consent
排除标准
- •Three, or more exacerbations of lower respiratory disease in the past year requiring systemic corticosteroids, or one exacerbation requiring hospitalization in the past 6 months
- •Intubation for COPD, or other cause of respiratory failure in the past year
- •Use of immunosuppressive therapy including oral prednisone > 10mg per day other than aerosolized corticosteroids, anytime within three months prior to participation
- •Evidence for an opportunistic infection/colonization of the airways, i.e., non-bacterial
- •Evidence for systemic illness including hematologic disorders (defined by an absolute neutrophil count (ANC) < 4000 /mL and platelets < 120,000/mL), cirrhosis, or hepatic insufficiency (total bilirubin, or alkaline phosphatase > 1.5 x normal, serum glutamate oxaloacetate transaminase, or serum glutamate pyruvate transaminase > 1.2 x normal values), or a coagulopathy (INR > 1.4), seizure disorder
- •Evidence for renal insufficiency with a calculated creatinine clearance using the Cockcroft and Gault's method of < 80 ml/min for males and < 70 ml/min for females, or serum creatinine > 1.4 mg/dL.
- •Evidence of coronary artery disease by history, e.g., angina or history of myocardial infarction within the past 12 months, unless corrected by coronary artery bypass graft within < 5 years, and asymptomatic since
- •Evidence for systemic abnormal renal function manifested by uncontrolled hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure >90 mmHg), hyperkalemia (serum potassium > 5.0 meq/dl, and/or elevated serum potassium above the normal range for the subject's age)
- •Pregnancy or lactation, or inability to take contraception during and for 6 months following treatment
- •Positive HIV, or hepatitis B or C serology, or another active infection
- •Current or past history of cancer excluding basal or squamous cell skin cancer
- •Undiagnosed pulmonary nodule requiring diagnostic evaluation
- •Weight loss > 10% usual body weight over the past 6 months or a BMI < 18
- •Known hypersensitivity or allergy to cyclosporine
- •Concurrent participation in other clinical trials within the prior month
- •Known medical or psychological condition (severe personality disorder or mental illness) that would not permit the subject to complete the trial or sign informed consent
- •Autoimmune disorders or other disorders with suspected systemic immune involvement
- •Active smoking history or urinary cotinine > 2
- •Hypersensitivity to midazolam or narcotics which would not allow bronchoscopy sedation
- •Concurrent use of drugs with a known interaction with cyclosporine
研究组 & 干预措施
Cyclosporine
干预措施: Cyclosporine (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients - Number of Patients That Developed Infection Requiring Systemic Antibiotic Therapy
时间窗: 16 weeks
Clinical diagnosis of infection which requires systemic antibiotic therapy during the 16 week study interval at Week 2, 4, 6, 8, 10, 12 and 16. Outcome measured the number of subjects who developed an infection requiring systemic antibiotic therapy during the study treatment interval.
Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients - Number of Patients That Developed Renal Insufficiency
时间窗: 16 weeks
Development of renal insufficiency defined as \> 30% elevation in serum creatinine above baseline which required dose modification of the cyclosporine over 16 week treatment interval at Week 2, 4, 6, 8, 10, 12 and 16. Outcome measured the number of subjects who developed renal insufficiency during the study treatment interval.
Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients- Nephrotoxicity - Measured by Serum Creatinine
时间窗: 16 weeks
Measurement of nephrotoxicity by monitoring serum creatinine over 16 week treatment interval. Mean serum creatinine values were assessed at Week 2, 4, 6, 8, 10, 12 and 16. The mean values of all measurements for each participant were calculated and then the mean across participants was calculated. Values expressed as mean ± SD.
次要结局
- Peripheral Blood T Cell Biomarkers Over 16 Week Treatment Interval - Change in the Percentage of Cluster of Differentiation 8 and Cluster of Differentiation 28(at Week 8 and Week 16)
- Peripheral Blood T Cell Biomarkers Over 16 Week Treatment Interval - Change in the Percentage of Cluster of Differentiation 4 (CD4)(at Week 8 and Week 16)
- Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 8 and Major Histocompatibility Complex II(at Week 8 and Week 16)
- Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 8+ Interferon Gamma(at Week 8 and Week 16)
- Pharmacokinetic - Pharmacodynamic Relationship of Oral Cyclosporine and Biomarkers of an Adaptive Immune Response - Cyclosporine Blood Levels(16 weeks)
- Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 4+ Interleukin-2(at Week 8 and Week 16)
- Effects of Cyclosporin A on Respiratory Function - Change in the Percentage of Post Predicted Value of Forced Vital Capacity(at Week 8 and Week 16)
- Effects of Cyclosporin A on Respiratory Function - Change in Exercise Capacity by a Shuttle Walk Distance Measured in Feet(at Week 8 and Week 16)
- Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 8+ Tumor Necrosis Factor(at Week 8 and Week 16)
- Effects of Cyclosporin A on Respiratory Function - Change in the Percentage of Post Predicted Value of Forced Expiratory Volume in 1 Second(at Week 8 and Week 16)
- Effects of Cyclosporin A on Symptoms - Change in Scores on a Shortness of Breath Scale(at Week 8 and Week 16)
研究者
Michael Donahoe
Professor
University of Pittsburgh