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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cyclosporine | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cyclosporine | Drug | Fifteen patients will receive cyclosporine at an initial dosing of 3.0 mg/kg/day. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients- Nephrotoxicity - Measured by Serum Creatinine | 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 | 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 | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic - Pharmacodynamic Relationship of Oral Cyclosporine and Biomarkers of an Adaptive Immune Response - Cyclosporine Blood Levels | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Donahoe, MD | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pittsburgh | Pittsburgh | Pennsylvania | 15213 | United States |
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
Patients were recruited from local clinics, advertisement, and a disease specific registry
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| ID | Title | Description |
|---|---|---|
| FG000 | Cyclosporine | Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine |
| FG001 | Placebo | Randomized to placebo capsules identical in appearance to cyclosporine |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cyclosporine | Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine |
| BG001 | Placebo | Randomized to placebo capsules identical in appearance to cyclosporine |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients- Nephrotoxicity - Measured by Serum Creatinine | 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. | Posted | Mean | Standard Deviation | mg / dL | 16 weeks |
|
Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cyclosporine | Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Renal insufficiency | Renal and urinary disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael Donahoe MD | University of Pittsburgh Medical Center | 412-648-9636 | donahoem@upmc.edu |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| D016572 | Cyclosporine |
| ID | Term |
|---|---|
| D003524 | Cyclosporins |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
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| Placebo | Drug | Fifteen patients will receive will receive placebo. |
|
| Peripheral Blood T Cell Biomarkers Over 16 Week Treatment Interval - Change in the Percentage of Cluster of Differentiation 4 (CD4) | 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 |
| Peripheral Blood T Cell Biomarkers Over 16 Week Treatment Interval - Change in the Percentage of Cluster of Differentiation 8 and Cluster of Differentiation 28 | 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). | at Week 8 and Week 16 |
| Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 8 and Major Histocompatibility Complex II | 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). | 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 | 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 | 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). | at Week 8 and Week 16 |
| Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 8+ Tumor Necrosis Factor | 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). | at Week 8 and Week 16 |
| Effects of Cyclosporin A on Respiratory Function - Change in the Percentage of Post Predicted Value of Forced Vital Capacity | 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). | 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 | 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 | 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). | at Week 8 and Week 16 |
| Effects of Cyclosporin A on Symptoms - Change in Scores on a Shortness of Breath Scale | 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 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Forced Vital Capacity (%) | Median | Inter-Quartile Range | % predicted |
|
| Forced Expiratory Volume 1 second (%) | Median | Full Range | % predicted |
|
| Functional Residual Capacity (%) | Median | Full Range | % predicted |
|
| Total Lung Capacity (%) | Median | Full Range | % predicted |
|
| Partial pressure of carbon dioxide (pCO2) | Mean | Standard Deviation | mm Hg |
|
| Partial pressure of oxygen (pO2) | Mean | Standard Deviation | mm Hg |
|
| Weight | Median | Full Range | kilograms |
|
| Systolic blood pressure (mm Hg) | Median | Full Range | mm Hg |
|
| Diastolic blood pressure (mm Hg) | Median | Full Range | mm Hg |
|
| White blood cell count | Mean | Standard Deviation | x10E ^09/L |
|
| Hemoglobin | Mean | Standard Deviation | grams / dL |
|
| Blood Urea Nitrogen | Mean | Standard Deviation | mg / dL |
|
| Creatinine | Mean | Standard Deviation | mg / dL |
|
| Glucose | Mean | Standard Deviation | mg / dL |
|
| Cholesterol | Mean | Standard Deviation | mg / dL |
|
|
|
| Primary | Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients - Number of Patients That Developed Renal Insufficiency | 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. | Posted | Count of Participants | Participants | 16 weeks |
|
|
|
| Primary | 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 | 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. | Posted | Count of Participants | Participants | 16 weeks |
|
|
|
| Secondary | Pharmacokinetic - Pharmacodynamic Relationship of Oral Cyclosporine and Biomarkers of an Adaptive Immune Response - Cyclosporine Blood Levels | 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). | Cyclosporine blood levels were not analyzed in placebo group. | Posted | Median | Full Range | ng/mL | 16 weeks |
|
|
|
| Secondary | Peripheral Blood T Cell Biomarkers Over 16 Week Treatment Interval - Change in the Percentage of Cluster of Differentiation 4 (CD4) | 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). | Posted | Median | Full Range | % of cells expressing biomarkers | at Week 8 and Week 16 |
|
|
|
| Secondary | Peripheral Blood T Cell Biomarkers Over 16 Week Treatment Interval - Change in the Percentage of Cluster of Differentiation 8 and Cluster of Differentiation 28 | 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). | Posted | Median | Full Range | % of cells expressing biomarkers | at Week 8 and Week 16 |
|
|
|
| Secondary | Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 8 and Major Histocompatibility Complex II | 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). | Posted | Median | Full Range | % of cells expressing biomarkers | at Week 8 and Week 16 |
|
|
|
| Secondary | Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 8+ Interferon Gamma | 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). | Posted | Median | Full Range | % of cells expressing biomarkers | at Week 8 and Week 16 |
|
|
|
| Secondary | Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 4+ Interleukin-2 | 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). | Posted | Median | Full Range | % of cells expressing biomarkers | at Week 8 and Week 16 |
|
|
|
| Secondary | Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 8+ Tumor Necrosis Factor | 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). | Posted | Median | Full Range | % of cells expressing biomarkers | at Week 8 and Week 16 |
|
|
|
| Secondary | Effects of Cyclosporin A on Respiratory Function - Change in the Percentage of Post Predicted Value of Forced Vital Capacity | 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). | Posted | Median | Full Range | Percentage of post predicted value | at Week 8 and Week 16 |
|
|
|
| Secondary | Effects of Cyclosporin A on Respiratory Function - Change in the Percentage of Post Predicted Value of Forced Expiratory Volume in 1 Second | 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). | Posted | Median | Full Range | Percentage of post predicted value | at Week 8 and Week 16 |
|
|
|
| Secondary | Effects of Cyclosporin A on Respiratory Function - Change in Exercise Capacity by a Shuttle Walk Distance Measured in Feet | 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). | Posted | Median | Full Range | feet | at Week 8 and Week 16 |
|
|
|
| Secondary | Effects of Cyclosporin A on Symptoms - Change in Scores on a Shortness of Breath Scale | 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). | Posted | Median | Full Range | units on a scale | at Week 8 and Week 16 |
|
|
|
| 0 |
| 8 |
| 0 |
| 8 |
| 6 |
| 8 |
| EG001 | Placebo | Randomized to placebo capsules identical in appearance to cyclosporine | 0 | 9 | 0 | 9 | 5 | 9 |
| Gastrointestinal upset | Gastrointestinal disorders | Non-systematic Assessment |
|
| Hyperkalemia | Renal and urinary disorders | Systematic Assessment |
|
| Hypertension | Renal and urinary disorders | Systematic Assessment |
|
| Tremor | Nervous system disorders | Non-systematic Assessment |
|
| Muscle cramp | Nervous system disorders | Non-systematic Assessment |
|
| Respiratory colonization | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Development of new respiratory system colonization without evidence for infection |
|
| Respiratory Infection -Bronchitis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Pulmonary nodule | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
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| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010455 |
| Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |