Oral Cyclosporine in Chronic Obstructive Pulmonary Disease

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Cyclosporine; Drug: Placebo	Phase 1; Phase 2

Study Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	43 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	A Randomized, Double-Blinded, Placebo-Controlled Protocol of Oral Cyclosporine in Patients With Advanced Stage Chronic Obstructive Pulmonary Disease
Study Start Date :	September 2009
Actual Primary Completion Date :	December 2016
Actual Study Completion Date :	December 2016

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: Cyclosporine	Drug: Cyclosporine; The study population (n=30) will be divided into two patient cohorts intended to receive cyclosporine at an initial dosing of 3.0 mg/kg/day or placebo, in a randomized ratio of 1:1.; Other Name: Neoral
Placebo Comparator: Placebo	Drug: Placebo; The study population (n=30) will be divided into two patient cohorts intended to receive cyclosporine at an initial dosing of 3.0 mg/kg/day or placebo, in a randomized ratio of 1:1.

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. To identify the safety profile of oral CsA immunotherapy in advanced stage COPD patients, with particular attention to nephrotoxicity, infection risk, and other recognized calcineurin toxicities. [ Time Frame: 16 weeks ]

Secondary Outcome Measures :

1. To identify the pharmacokinetic-pharmacodynamic relationships of oral CsA using sparse blood sampling measures of drug exposure and biomarkers of an adaptive immune response as endpoints in subjects with advanced stage COPD. [ Time Frame: 16 weeks ]
2. To explore the effects of CsA on respiratory function, symptoms, quantitative computed tomographic indices, and markers of bone metabolism. [ Time Frame: 16 weeks ]

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	45 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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 FEV1 will include 25% ≤FEV1 ≤ 60%
• Subjects agree to maintain a stable medication regimen in the absence of a disease flare
• ECOG performance status of 0, 1, or 2
• pCO2 < 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, SGOT, or SGPT > 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 CABG within < 5 years, and asymptomatic since
• Evidence for systemic abnormal renal function manifested by uncontrolled hypertension (systolic blood pressure > 160mmHg or diastolic blood pressure >90mmHg), 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

Contacts and Locations

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213

Sponsors and Collaborators

Michael Donahoe

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:	Michael Donahoe, MD	University of Pittsburgh

More Information

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Michael Donahoe, Professor, University of Pittsburgh
ClinicalTrials.gov Identifier:	NCT00974142 History of Changes
Other Study ID Numbers:	PRO09050330
First Posted:	September 10, 2009
Last Update Posted:	October 5, 2017
Last Verified:	October 2017

Keywords provided by Michael Donahoe, University of Pittsburgh:

COPD; Chronic Obstructive Pulmonary Disease; Cyclosporine; Oral Immunotherapy; Advanced stage

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Cyclosporins; Cyclosporine; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action	Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antifungal Agents; Anti-Infective Agents; Dermatologic Agents; Antirheumatic Agents; Calcineurin Inhibitors