COPD, Chronic Bronchitis
Conditions
Brief summary
The purpose of this study is to evaluate the effect of Losartan on cigarette smoke-induced lung injury in smokers and ex-smokers with and without chronic obstructive pulmonary disease (COPD).
Interventions
DRUGLosartan 50 mg
50 mg Losartan taken orally once daily for 4 consecutive weeks.
DRUGLosartan 100 mg
50 mg Losartan taken orally twice daily for 4 consecutive weeks.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Flight Attendant Medical Research Institute
University of Miami
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
35 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
1. Fulfill one of the group definitions above 2. Age between 35 and 75 years old 3. Clinical diagnosis of chronic bronchitis, defined as productive cough for at least 3 months per year for at least two consecutive years 4. Stable maintenance of all current medication therapy for 3 months, including ARBs for treated groups
Exclusion criteria
1. Current therapy with Angiotensin-converting-enzyme (ACE) inhibitor,or Intolerance to Angiotensin II receptor blockers (ARB) 2. Women of child bearing potential 3. Current use of nonsteroidal antiinflammatory drugs or potassium supplementation, treatment with aliskiren, anticoagulation 4. COPD exacerbation requiring treatment within 6 weeks of the screening visit 5. Oral corticosteroid use within 6 weeks of the screening visit 6. Significant hypoxemia (oxygen saturation \<90% on room air), chronic respiratory failure by history (pCO2 \> 45 mmHg) and forced expiratory volume in 1 second (FEV1) below 40%, clinical evidence of cor pulmonale 7. Untreated arterial hypertension (systolic blood pressure \>140 mm Hg, diastolic blood pressure \> 90 mm Hg) 8. Ability to understand and willingness to sign consent documents 9. Blood pressure less than 100 mm Hg systolic or 70 mm Hg diastolic while standing at the screening visit 10. Cardiac, renal, hepatic (LFTs \> 3x normal upper limit), neurological, psychiatric, endocrine or neoplastic diseases that are at the discretion of the investigator, to interfere with participation in study 11. History of renal artery stenosis 12. Concomitant airway disorders other than COPD and chronic bronchitis, such as bronchiectasis and asthma (history and reversible airflow obstruction by American Thoracic Society (ATS) criteria) 13. History of pulmonary malignancies, and any other malignancies in the last 5 years 14. History of thoracic surgery. 15. Acute pulmonary exacerbation within 6 weeks from the Screening Visit. 16. Subjects with no airflow obstruction by spirometry but with a decrease in diffusing capacity of lung for carbon monoxide(DLco) possibly indicating emphysema. 17. Significant exposure to environmental tobacco smoke or atmospheric or occupational pollutants 18. Urine pregnancy positive test at the Screening Visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Nasal Potential Difference (NPD). | Baseline, 8 weeks | NPD were assessed from nasal cells collected using sterile cytology brushes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in IL-8 Concentrations | Baseline, 8 weeks | Interleukin (IL)-8 concentrations were analyzed from samples on nasal lavage |
| Percent Change in TGF-ß mRNA Expression | Baseline, 8 weeks | Transforming Growth Factor (TGF)-ß messenger ribonucleic acid (mRNA) expression were analyzed from nasal cells samples. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Non-smokers 10 healthy non-smokers will receive 50 mg of losartan for 4 weeks followed by 100 mg of losartan for 4 weeks
Losartan 50 mg: 50 mg QD for 4 weeks
losartan 100 mg: 50 mg BID for 4 weeks | 16 |
| Smokers Without COPD 10 smokers without COPD will receive 50 mg of losartan for 4 weeks followed by 100 mg of losartan for 4 weeks
Losartan 50 mg: 50 mg QD for 4 weeks
losartan 100 mg: 50 mg BID for 4 weeks | 15 |
| Ex-smokers With COPD 10 ex-smokers with COPD will receive 50 mg of losartan for 4 weeks followed by 100 mg of losartan for 4 weeks
Losartan 50 mg: 50 mg QD for 4 weeks
losartan 100 mg: 50 mg BID for 4 weeks | 0 |
| Total | 31 |
Baseline characteristics
| Characteristic | Healthy Non-smokers | Smokers Without COPD | Ex-smokers With COPD | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 15 Participants | 0 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 13 Participants | 0 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 2 Participants | 0 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) White | 13 Participants | 9 Participants | 0 Participants | 22 Participants |
| Sex: Female, Male Female | 13 Participants | 8 Participants | 0 Participants | 21 Participants |
| Sex: Female, Male Male | 3 Participants | 7 Participants | 0 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 15 | 0 / 0 |
| other Total, other adverse events | 0 / 16 | 0 / 15 | 0 / 0 |
| serious Total, serious adverse events | 0 / 16 | 0 / 15 | 0 / 0 |
Outcome results
Primary
Change in Nasal Potential Difference (NPD).
NPD were assessed from nasal cells collected using sterile cytology brushes.
Time frame: Baseline, 8 weeks
Population: Nasal sample data for all participants were not available as the readings were uninterpretable and not further analyzed.
Secondary
Change in IL-8 Concentrations
Interleukin (IL)-8 concentrations were analyzed from samples on nasal lavage
Time frame: Baseline, 8 weeks
Population: No participants were recruited in the Ex-Smokers with COPD due to difficulty in recruitment prior to study termination. Only 5 participants were analyzed for the Healthy Non-Smokers and Smokers without COPD arms as only 5 in each group had complete sets of samples that could be analyzed due to bad quality/quantity available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Non-smokers | Change in IL-8 Concentrations | 2867 pg/mL | Standard Deviation 1685 |
| Smokers Without COPD | Change in IL-8 Concentrations | 4676 pg/mL | Standard Deviation 1948 |
Secondary
Percent Change in TGF-ß mRNA Expression
Transforming Growth Factor (TGF)-ß messenger ribonucleic acid (mRNA) expression were analyzed from nasal cells samples.
Time frame: Baseline, 8 weeks
Population: No participants were recruited in the Ex-Smokers with COPD due to difficulty in recruitment prior to study termination. Only 5 participants were analyzed for the Healthy Non-Smokers and Smokers without COPD arms as only 5 in each group had complete sets of samples that could be analyzed due to bad quality/quantity available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Non-smokers | Percent Change in TGF-ß mRNA Expression | -51 percentage change in mRNA expression | Standard Deviation 31 |
| Smokers Without COPD | Percent Change in TGF-ß mRNA Expression | -23 percentage change in mRNA expression | Standard Deviation 70 |