Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, inhaled steroids, gene expression, smoker's lungs
Brief summary
The purpose of this study is to assess the effect of inhaled beclomethasone (an inhaled corticosteroid) on the pattern of the lung airway epithelium and alveolar macrophages gene expression of healthy smokers. We hypothesize that the administration of beclomethasone will result in reversibility of some of the airway epithelium and alveolar macrophage gene expression changes induced by cigarette smoking.
Detailed description
The study will involve healthy smokers and non smokers enrolled in IRB approved protocol #0005004439 entitled Evaluation of the Lungs of Normal (Smokers, Ex-smokers, Non-Smokers) Individuals with Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing, and Bronchial Wall Biopsy. They will be invited to participate in this protocol only if they meet the additional inclusion/exclusion criteria of this protocol (see inclusion/exclusion criteria, section A6). The Principal Investigator, Ann E. Tilley, MD or authorized representative will obtain consent from individuals for this study. Once enrolled, smokers will be randomized to either the treated smoker group \[320 micrograms (mcg) of beclomethasone; 2 puffs twice a day (each puff delivers 80 mcg) for 7 days\] or non-treated group. Beclomethasone is available as a metered dose inhaler \[QVAR(TEVA Pharmaceuticals)\] delivering 80 micrograms (mcg) of beclomethasone per one puff. We will be using QVAR HFA (TEVA Pharmaceuticals), which delivers 80 mcg per puff. QVAR will be purchased by the Department of Genetic Medicine. It will be dispensed as appropriate to each research subject recruited in the trial at the Department of Genetic Medicine at 1305 York Ave YAB-13th floor, New York, NY 10021 (a facility of Weill Medical College). It will be stored at The Arthur & Rochelle Belfer Gene Therapy Core Facility located at 515 E. 71st St., S901, New York, NY 10021 under the supervision of Stephen Kaminksy, PhD, Co-Director of the GMP (Good Manufacturing Practice). Each study individual will receive 1 package of the study medication which consists of 1 canister of QVAR 80 MDI (metered dose inhaler). Non-smokers, defined as individuals who have never smoked, will act as control like the Non-Treated Smoker group and receive no treatment. For all subjects, the screening, baseline bronchoscopy, and the bronchoscopies on Days 7±3 and 14±3 tests will be performed as part of IRB approved protocol #0005004439. No additional bronchoscopies will be performed under the current protocol.
Interventions
DRUGBeclomethasone
The treatment with inhaled beclomethasone will be administered to Group A from Day 1 to Day 7 via a metered dose inhaler (QVAR 80 HFA) delivering 80 micrograms of beclomethasone per puff. QVAR will be purchased by the Department of Genetic Medicine. The dose will be 2 puffs twice a day for 7 days
Sponsors
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
All Smokers (Treated and Non-Treated) * All study individual should be enrolled in Weill-IRB protocol #0005004439 entitled Evaluation of the Lungs of Normal (Smokers, Ex-smokers, Non-Smokers) Individuals with Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing, and Bronchial Wall Biopsy * All study subjects should be able to provide informed consent * Current smokers with 15-to 40 pack-year history * All study individuals should be healthy as per protocol #0005004439 entitled Evaluation of the Lungs of Normal (Smokers, Ex-smokers, Non-Smokers) Individuals with Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing, and Bronchial Wall Biopsy Non-Smokers * All study individual should be enrolled in Weill-IRB protocol #0005004439 entitled Evaluation of the Lungs of Normal (Smokers, Ex-smokers, Non-Smokers) Individuals with Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing, and Bronchial Wall Biopsy * All study subjects should be able to provide informed consent * All study individual should be healthy as per protocol #0005004439 entitled Evaluation of the Lungs of Normal (Smokers, Ex-smokers, Non-Smokers) Individuals with Segmental Bronchopulmonary Lung Lavage, Bronchial Brushing, and Bronchial Wall Biopsy
Exclusion criteria
All Smokers * Smokers intending to quit smoking in the next 14 days. * Individuals already receiving any lung related inhalers * Females who are pregnant or nursing Non-Smokers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With A Significant Change in Gene Expression in the Airway Epithelium and Alveolar Macrophages at Days 7 and 14 | Analysis will be done on samples collected on Day 7 and Day 14 following initiation of therapy compared to baseline values obtained on the day prior to initiation of treatment. | The primary study endpoint is a change in the gene expression in the airway epithelium or alveolar macrophages of healthy smokers following treatment with beclomethasone. Airway epithelium and alveolar macrophages are processed to yield high quality RNA. Complementary DNA (cDNA) is transcribed from the RNA in vitro and the product is hybridized onto gene microarray chips. The chip is then scanned and the image analyzed using the Affymetrix Microarray suite version 5 (MAS5) algorithm. Using GeneSpring software the data is normalized and differential expression is determined by fold change (up or down regulation) of the individual genes by comparing the geometric mean expression value from the airway epithelium and alveolar macrophages obtained from Day 7 and Day 14 following initiation of therapy to baseline values. |
Countries
United States
Participant flow
Pre-assignment details
24 subjects underwent informed consent and enrolled into the study. 2 smoker subjects screen-failed (recent illicit drug use history of myocardial infarction). These individuals were dropped from the study prior to randomization, therefore only 22 individuals were assigned into one of the three study groups.
Participants by arm
| Arm | Count |
|---|---|
| Treated Smokers The treatment with inhaled beclomethasone will be administered to Treated Smokers from Day 1 to Day 7 via a metered dose inhaler (QVAR 80 HFA) delivering 80 micrograms of beclomethasone per puff. QVAR will be purchased by the Department of Genetic Medicine. The dose will be 2 puffs twice a day for 7 days. | 6 |
| Non-Treated Smokers Non-Treated Smokers will act as a control and includes healthy smokers who received no treatment. | 4 |
| Non-smokers Non-Smokers will act as a control and includes healthy non-smokers who received no treatment. | 12 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Samples Did Not pass QC | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Treated Smokers | Non-Treated Smokers | Non-smokers | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 4 Participants | 12 Participants | 22 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 7 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 5 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 4 | 0 / 12 |
| other Total, other adverse events | 0 / 6 | 0 / 4 | 0 / 12 |
| serious Total, serious adverse events | 0 / 6 | 0 / 4 | 0 / 12 |
Outcome results
Primary
Number of Participants With A Significant Change in Gene Expression in the Airway Epithelium and Alveolar Macrophages at Days 7 and 14
The primary study endpoint is a change in the gene expression in the airway epithelium or alveolar macrophages of healthy smokers following treatment with beclomethasone. Airway epithelium and alveolar macrophages are processed to yield high quality RNA. Complementary DNA (cDNA) is transcribed from the RNA in vitro and the product is hybridized onto gene microarray chips. The chip is then scanned and the image analyzed using the Affymetrix Microarray suite version 5 (MAS5) algorithm. Using GeneSpring software the data is normalized and differential expression is determined by fold change (up or down regulation) of the individual genes by comparing the geometric mean expression value from the airway epithelium and alveolar macrophages obtained from Day 7 and Day 14 following initiation of therapy to baseline values.
Time frame: Analysis will be done on samples collected on Day 7 and Day 14 following initiation of therapy compared to baseline values obtained on the day prior to initiation of treatment.
Population: Subjects underwent bronchoscopy procedure at 7 and 14 days after baseline to collect samples including small airway epithelium and alveolar macrophages.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treated Smokers | Number of Participants With A Significant Change in Gene Expression in the Airway Epithelium and Alveolar Macrophages at Days 7 and 14 | Small Airway Epithelium | 0 Participants |
| Treated Smokers | Number of Participants With A Significant Change in Gene Expression in the Airway Epithelium and Alveolar Macrophages at Days 7 and 14 | Alveolar Macrophages | 0 Participants |
| Non-Treated Smokers | Number of Participants With A Significant Change in Gene Expression in the Airway Epithelium and Alveolar Macrophages at Days 7 and 14 | Small Airway Epithelium | NA Participants |
| Non-Treated Smokers | Number of Participants With A Significant Change in Gene Expression in the Airway Epithelium and Alveolar Macrophages at Days 7 and 14 | Alveolar Macrophages | NA Participants |
| Non-Smokers | Number of Participants With A Significant Change in Gene Expression in the Airway Epithelium and Alveolar Macrophages at Days 7 and 14 | Small Airway Epithelium | NA Participants |
| Non-Smokers | Number of Participants With A Significant Change in Gene Expression in the Airway Epithelium and Alveolar Macrophages at Days 7 and 14 | Alveolar Macrophages | NA Participants |