Oral Cyclosporine in Chronic Obstructive Pulmonary Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00974142
Recruitment Status : Completed
First Posted : September 10, 2009
Last Update Posted : October 5, 2017
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Michael Donahoe, University of Pittsburgh

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 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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: COPD Lung Diseases
U.S. FDA Resources

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.

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 ]

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00974142

United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Michael Donahoe
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Michael Donahoe, MD University of Pittsburgh

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

Keywords provided by Michael Donahoe, University of Pittsburgh:
Chronic Obstructive Pulmonary Disease
Oral Immunotherapy
Advanced stage

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
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