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Oral Cyclosporine in Chronic Obstructive Pulmonary Disease

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ClinicalTrials.gov Identifier: NCT00974142
Recruitment Status : Completed
First Posted : September 10, 2009
Results First Posted : May 9, 2018
Last Update Posted : May 9, 2018
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Michael Donahoe, University of Pittsburgh

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Chronic Obstructive Pulmonary Disease
Interventions Drug: Cyclosporine
Drug: Placebo
Enrollment 43
Recruitment Details Patients were recruited from local clinics, advertisement, and a disease specific registry
Pre-assignment Details 772 patients underwent initial screening and 43 were eligible to sign consent. These patients underwent a second 2 week screening process and 17 subjects met all criteria for randomization
Arm/Group Title Cyclosporine Placebo
Hide Arm/Group Description Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine Randomized to placebo capsules identical in appearance to cyclosporine
Period Title: Overall Study
Started 8 9
Completed 8 9
Not Completed 0 0
Arm/Group Title Cyclosporine Placebo Total
Hide Arm/Group Description Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine Randomized to placebo capsules identical in appearance to cyclosporine Total of all reporting groups
Overall Number of Baseline Participants 8 9 17
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 8 participants 9 participants 17 participants
68
(55 to 79)
63
(48 to 77)
67
(48 to 79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 9 participants 17 participants
Female
2
  25.0%
4
  44.4%
6
  35.3%
Male
6
  75.0%
5
  55.6%
11
  64.7%
Forced Vital Capacity (%)  
Median (Inter-Quartile Range)
Unit of measure:  % predicted
Number Analyzed 8 participants 9 participants 17 participants
88
(71 to 105)
77
(60 to 94)
79
(60 to 105)
Forced Expiratory Volume 1 second (%)  
Median (Full Range)
Unit of measure:  % predicted
Number Analyzed 8 participants 9 participants 17 participants
38
(31 to 54)
43
(27 to 58)
39
(27 to 58)
Functional Residual Capacity (%)  
Median (Full Range)
Unit of measure:  % predicted
Number Analyzed 8 participants 9 participants 17 participants
146
(108 to 180)
149
(81 to 170)
149
(81 to 180)
Total Lung Capacity (%)  
Median (Full Range)
Unit of measure:  % predicted
Number Analyzed 8 participants 9 participants 17 participants
123
(100 to 145)
119
(84 to 138)
119
(84 to 145)
Partial pressure of carbon dioxide (pCO2)  
Mean (Standard Deviation)
Unit of measure:  Mm Hg
Number Analyzed 8 participants 9 participants 17 participants
40  (3.6) 42.6  (3.9) 41.2  (3.7)
Partial pressure of oxygen (pO2)  
Mean (Standard Deviation)
Unit of measure:  Mm Hg
Number Analyzed 8 participants 9 participants 17 participants
71  (11) 76  (20) 74  (15)
Weight  
Median (Full Range)
Unit of measure:  Kilograms
Number Analyzed 8 participants 9 participants 17 participants
83
(60 to 105)
93
(55 to 119)
84
(55 to 119)
Systolic blood pressure (mm Hg)  
Median (Full Range)
Unit of measure:  Mm Hg
Number Analyzed 8 participants 9 participants 17 participants
141
(125 to 152)
133
(104 to 150)
138
(104 to 152)
Diastolic blood pressure (mm Hg)  
Median (Full Range)
Unit of measure:  Mm Hg
Number Analyzed 8 participants 9 participants 17 participants
82
(71 to 95)
78
(70 to 91)
79
(70 to 95)
White blood cell count  
Mean (Standard Deviation)
Unit of measure:  x10E ^09/L
Number Analyzed 8 participants 9 participants 17 participants
7.3  (1.3) 6.6  (2.0) 7.1  (2.2)
Hemoglobin  
Mean (Standard Deviation)
Unit of measure:  Grams / dL
Number Analyzed 8 participants 9 participants 17 participants
13.7  (1.0) 13.6  (0.9) 13.7  (1.03)
Blood Urea Nitrogen  
Mean (Standard Deviation)
Unit of measure:  Mg / dL
Number Analyzed 8 participants 9 participants 17 participants
16  (5.4) 13  (3.2) 13.4  (3.9)
Creatinine  
Mean (Standard Deviation)
Unit of measure:  Mg / dL
Number Analyzed 8 participants 9 participants 17 participants
0.9  (0.2) 0.9  (0.2) 0.9  (0.2)
Glucose  
Mean (Standard Deviation)
Unit of measure:  Mg / dL
Number Analyzed 8 participants 9 participants 17 participants
102  (13) 113  (29) 111  (29)
Cholesterol  
Mean (Standard Deviation)
Unit of measure:  Mg / dL
Number Analyzed 8 participants 9 participants 17 participants
183  (30) 193  (20) 183  (20)
1.Primary Outcome
Title Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients- Nephrotoxicity - Measured by Serum Creatinine
Hide Description 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.
Time Frame 16 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cyclosporine Placebo
Hide Arm/Group Description:
Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine
Randomized to placebo capsules identical in appearance to cyclosporine
Overall Number of Participants Analyzed 8 9
Mean (Standard Deviation)
Unit of Measure: mg / dL
0.94  (0.2) 0.88  (0.2)
2.Primary Outcome
Title Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients - Number of Patients That Developed Renal Insufficiency
Hide Description 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.
Time Frame 16 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cyclosporine Placebo
Hide Arm/Group Description:
Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine
Randomized to placebo capsules identical in appearance to cyclosporine
Overall Number of Participants Analyzed 8 9
Measure Type: Count of Participants
Unit of Measure: Participants
4
  50.0%
1
  11.1%
3.Primary Outcome
Title 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
Hide Description 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.
Time Frame 16 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cyclosporine Placebo
Hide Arm/Group Description:
Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine
Randomized to placebo capsules identical in appearance to cyclosporine
Overall Number of Participants Analyzed 8 9
Measure Type: Count of Participants
Unit of Measure: Participants
1
  12.5%
1
  11.1%
4.Secondary Outcome
Title Pharmacokinetic - Pharmacodynamic Relationship of Oral Cyclosporine and Biomarkers of an Adaptive Immune Response - Cyclosporine Blood Levels
Hide Description 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).
Time Frame 16 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Cyclosporine blood levels were not analyzed in placebo group.
Arm/Group Title Cyclosporine Placebo
Hide Arm/Group Description:
Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine
Randomized to placebo capsules identical in appearance to cyclosporine
Overall Number of Participants Analyzed 8 0
Median (Full Range)
Unit of Measure: ng/mL
147
(69 to 196)
5.Secondary Outcome
Title Peripheral Blood T Cell Biomarkers Over 16 Week Treatment Interval - Change in the Percentage of Cluster of Differentiation 4 (CD4)
Hide Description 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).
Time Frame at Week 8 and Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cyclosporine Placebo
Hide Arm/Group Description:
Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine
Randomized to placebo capsules identical in appearance to cyclosporine
Overall Number of Participants Analyzed 8 9
Median (Full Range)
Unit of Measure: % of cells expressing biomarkers
-3.1
(-18.8 to 3.5)
3.6
(-8.5 to 45.2)
6.Secondary Outcome
Title Peripheral Blood T Cell Biomarkers Over 16 Week Treatment Interval - Change in the Percentage of Cluster of Differentiation 8 and Cluster of Differentiation 28
Hide Description 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).
Time Frame at Week 8 and Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cyclosporine Placebo
Hide Arm/Group Description:
Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine
Randomized to placebo capsules identical in appearance to cyclosporine
Overall Number of Participants Analyzed 8 9
Median (Full Range)
Unit of Measure: % of cells expressing biomarkers
-0.78
(-19.2 to 6.3)
-1.6
(-6.6 to 3.0)
7.Secondary Outcome
Title Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 8 and Major Histocompatibility Complex II
Hide Description 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).
Time Frame at Week 8 and Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cyclosporine Placebo
Hide Arm/Group Description:
Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine
Randomized to placebo capsules identical in appearance to cyclosporine
Overall Number of Participants Analyzed 8 9
Median (Full Range)
Unit of Measure: % of cells expressing biomarkers
-2.4
(-11.2 to 7.2)
0.5
(-4.7 to 3.1)
8.Secondary Outcome
Title Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 8+ Interferon Gamma
Hide Description 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).
Time Frame at Week 8 and Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cyclosporine Placebo
Hide Arm/Group Description:
Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine
Randomized to placebo capsules identical in appearance to cyclosporine
Overall Number of Participants Analyzed 8 9
Median (Full Range)
Unit of Measure: % of cells expressing biomarkers
-4.1
(-24.1 to 49.6)
4.4
(-44.6 to 51.3)
9.Secondary Outcome
Title Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 4+ Interleukin-2
Hide Description 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).
Time Frame at Week 8 and Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cyclosporine Placebo
Hide Arm/Group Description:
Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine
Randomized to placebo capsules identical in appearance to cyclosporine
Overall Number of Participants Analyzed 8 9
Median (Full Range)
Unit of Measure: % of cells expressing biomarkers
-1.7
(-13.3 to 16.8)
4.7
(-15.6 to 11.1)
10.Secondary Outcome
Title Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 8+ Tumor Necrosis Factor
Hide Description 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).
Time Frame at Week 8 and Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cyclosporine Placebo
Hide Arm/Group Description:
Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine
Randomized to placebo capsules identical in appearance to cyclosporine
Overall Number of Participants Analyzed 8 9
Median (Full Range)
Unit of Measure: % of cells expressing biomarkers
0.0
(-52.6 to 9.8)
2.3
(-18 to 32.3)
11.Secondary Outcome
Title Effects of Cyclosporin A on Respiratory Function - Change in the Percentage of Post Predicted Value of Forced Vital Capacity
Hide Description 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).
Time Frame at Week 8 and Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cyclosporine Placebo
Hide Arm/Group Description:
Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine
Randomized to placebo capsules identical in appearance to cyclosporine
Overall Number of Participants Analyzed 8 9
Median (Full Range)
Unit of Measure: Percentage of post predicted value
-0.01
(-.04 to 0.6)
0.07
(-0.3 to 0.2)
12.Secondary Outcome
Title Effects of Cyclosporin A on Respiratory Function - Change in the Percentage of Post Predicted Value of Forced Expiratory Volume in 1 Second
Hide Description 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).
Time Frame at Week 8 and Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cyclosporine Placebo
Hide Arm/Group Description:
Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine
Randomized to placebo capsules identical in appearance to cyclosporine
Overall Number of Participants Analyzed 8 9
Median (Full Range)
Unit of Measure: Percentage of post predicted value
-0.02
(-0.3 to 0.3)
-0.02
(-0.2 to 0.1)
13.Secondary Outcome
Title Effects of Cyclosporin A on Respiratory Function - Change in Exercise Capacity by a Shuttle Walk Distance Measured in Feet
Hide Description 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).
Time Frame at Week 8 and Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cyclosporine Placebo
Hide Arm/Group Description:
Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine
Randomized to placebo capsules identical in appearance to cyclosporine
Overall Number of Participants Analyzed 8 9
Median (Full Range)
Unit of Measure: feet
230
(170 to 450)
220
(140 to 350)
14.Secondary Outcome
Title Effects of Cyclosporin A on Symptoms - Change in Scores on a Shortness of Breath Scale
Hide Description 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).
Time Frame at Week 8 and Week 16
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cyclosporine Placebo
Hide Arm/Group Description:
Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine
Randomized to placebo capsules identical in appearance to cyclosporine
Overall Number of Participants Analyzed 8 9
Median (Full Range)
Unit of Measure: units on a scale
39
(10 to 81)
39
(4 to 85)
Time Frame Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cyclosporine Placebo
Hide Arm/Group Description Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine Randomized to placebo capsules identical in appearance to cyclosporine
All-Cause Mortality
Cyclosporine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)      0/9 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Cyclosporine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/8 (0.00%)      0/9 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cyclosporine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/8 (75.00%)      5/9 (55.56%)    
Gastrointestinal disorders     
Gastrointestinal upset *  4/8 (50.00%)  4 0/9 (0.00%)  0
Nervous system disorders     
Tremor *  1/8 (12.50%)  1 0/9 (0.00%)  0
Muscle cramp *  1/8 (12.50%)  1 0/9 (0.00%)  0
Renal and urinary disorders     
Renal insufficiency   4/8 (50.00%)  4 1/9 (11.11%)  1
Hyperkalemia   2/8 (25.00%)  2 0/9 (0.00%)  0
Hypertension   1/8 (12.50%)  1 0/9 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Respiratory colonization  [1]  1/8 (12.50%)  1 1/9 (11.11%)  1
Respiratory Infection -Bronchitis *  1/8 (12.50%)  1 1/9 (11.11%)  1
Pulmonary nodule   0/8 (0.00%)  0 1/9 (11.11%)  1
Dyspnea   0/8 (0.00%)  0 1/9 (11.11%)  1
*
Indicates events were collected by non-systematic assessment
Indicates events were collected by systematic assessment
[1]
Development of new respiratory system colonization without evidence for infection
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Michael Donahoe MD
Organization: University of Pittsburgh Medical Center
Phone: 412-648-9636
Responsible Party: Michael Donahoe, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00974142     History of Changes
Other Study ID Numbers: PRO09050330
First Submitted: September 9, 2009
First Posted: September 10, 2009
Results First Submitted: January 3, 2018
Results First Posted: May 9, 2018
Last Update Posted: May 9, 2018