Oral Cyclosporine in Chronic Obstructive Pulmonary Disease

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00974142
First received: September 9, 2009
Last updated: November 20, 2013
Last verified: November 2013
  Purpose

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 Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: Cyclosporine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • To explore the effects of CsA on respiratory function, symptoms, quantitative computed tomographic indices, and markers of bone metabolism. [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 43
Study Start Date: September 2009
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   45 Years to 80 Years
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00974142

Locations
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Michael Donahoe, MD University of Pittsburgh
  More Information

No publications provided

Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00974142     History of Changes
Other Study ID Numbers: PRO09050330
Study First Received: September 9, 2009
Last Updated: November 20, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
COPD
Chronic Obstructive Pulmonary Disease
Cyclosporine
Oral Immunotherapy
Advanced stage

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Cyclosporins
Cyclosporine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on April 15, 2014