- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00974142
Oral Cyclosporine in Chronic Obstructive Pulmonary Disease
A Randomized, Double-Blinded, Placebo-Controlled Protocol of Oral Cyclosporine in Patients With Advanced Stage Chronic Obstructive Pulmonary Disease
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15213
- University of Pittsburgh
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
PLACEBO_COMPARATOR: Placebo
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Fifteen patients will receive will receive placebo.
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EXPERIMENTAL: Cyclosporine
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Fifteen patients will receive cyclosporine at an initial dosing of 3.0 mg/kg/day.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients- Nephrotoxicity - Measured by Serum Creatinine
Time Frame: 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.
|
16 weeks
|
Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients - Number of Patients That Developed Renal Insufficiency
Time Frame: 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.
|
16 weeks
|
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
Time Frame: 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.
|
16 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetic - Pharmacodynamic Relationship of Oral Cyclosporine and Biomarkers of an Adaptive Immune Response - Cyclosporine Blood Levels
Time Frame: 16 weeks
|
Cyclosporine blood levels on therapy over 16 week treatment interval were measured at Weeks 2, 4, 6, 8, 10, 12 & 16.
The median for each participant was found and then the overall median was determined.
Values expressed as median (full range).
|
16 weeks
|
Peripheral Blood T Cell Biomarkers Over 16 Week Treatment Interval - Change in the Percentage of Cluster of Differentiation 4 (CD4)
Time Frame: at Week 8 and Week 16
|
Outcome measured the change in the percentage of cluster of differentiation 4 (CD4) at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16).
Values expressed as median (full range).
|
at Week 8 and Week 16
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Peripheral Blood T Cell Biomarkers Over 16 Week Treatment Interval - Change in the Percentage of Cluster of Differentiation 8 and Cluster of Differentiation 28
Time Frame: at Week 8 and Week 16
|
Outcome measured the change in the percentage of peripheral blood T cell biomarkers - cluster of differentiation 8 (CD8), cluster of differentiation 28 (CD28) at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16).
Values expressed as median (full range).
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at Week 8 and Week 16
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Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 8 and Major Histocompatibility Complex II
Time Frame: at Week 8 and Week 16
|
Outcome measured the change in the percentage of peripheral blood cells expressing biomarker - cluster of differentiation 8 (CD8), major histocompatibility complex (MHC) II at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16).
Values expressed as median (full range).
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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
Time Frame: at Week 8 and Week 16
|
Outcome measured the change in the percentage of peripheral blood T cell biomarkers - CD8+interferon gamma at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16).
Values expressed as median (full range).
|
at Week 8 and Week 16
|
Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 4+ Interleukin-2
Time Frame: at Week 8 and Week 16
|
Outcome measured the change in the percentage of peripheral blood T cell biomarkers - cluster of differentiation 4+ interleukin-2 at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16).
Values expressed as median (full range).
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at Week 8 and Week 16
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Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 8+ Tumor Necrosis Factor
Time Frame: at Week 8 and Week 16
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Outcome measured the change in the percentage of peripheral blood T cell biomarkers - CD8+ tumor necrosis factor at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16).
Values expressed as median (full range).
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at Week 8 and Week 16
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Effects of Cyclosporin A on Respiratory Function - Change in the Percentage of Post Predicted Value of Forced Vital Capacity
Time Frame: at Week 8 and Week 16
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Outcome measured the change in the percentage of post predicted value of forced vital capacity at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16).
Values expressed as median (full range).
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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
Time Frame: at Week 8 and Week 16
|
Outcome measured the change in the percentage of post predicted value of forced expiratory volume in 1 second at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16).
Values expressed as median (full range).
|
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
Time Frame: at Week 8 and Week 16
|
Measurement of exercise capacity by a shuttle walk distance measured in feet at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16).
The purpose of the shuttle walk test is to see how far and fast a patient can walk (without stopping for a rest) by following a series of time signals.Values expressed as median (full range).
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at Week 8 and Week 16
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Effects of Cyclosporin A on Symptoms - Change in Scores on a Shortness of Breath Scale
Time Frame: at Week 8 and Week 16
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Scores on a shortness of breath scale (University of California at San Diego Dyspnea scale): shortness of breath questionnaire scores are summed as a total score ranging from 0-120 with higher scores indicating more severe breathlessness.
Assessments were performed at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16).
Values expressed as median (full range).
|
at Week 8 and Week 16
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Lung Diseases
- Lung Diseases, Obstructive
- Pulmonary Disease, Chronic Obstructive
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Antifungal Agents
- Calcineurin Inhibitors
- Cyclosporine
- Cyclosporins
Other Study ID Numbers
- PRO09050330
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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