Oral Cyclosporine in Chronic Obstructive Pulmonary Disease

Michael Donahoe

Status and phase

Completed

Phase 2

Phase 1

Conditions

Chronic Obstructive Pulmonary Disease

Treatments

Drug: Placebo

Drug: Cyclosporine

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00974142

PRO09050330

Details and patient eligibility

About

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.

Enrollment

43 patients

Sex

All

Ages

45 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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