Effect of Losartan on Airway Mucociliary Dysfunction in Patients With COPD and Chronic Bronchitis
Trial Snapshot
- Phase
- Phase 4
- Status
- Terminated
- Sponsor
- University of Miami
- Enrollment
- 31
- Locations
- 1
- Primary Endpoint
- Change in Nasal Potential Difference (NPD).
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 35 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Fulfill one of the group definitions above
- •Age between 35 and 75 years old
- •Clinical diagnosis of chronic bronchitis, defined as productive cough for at least 3 months per year for at least two consecutive years
- •Stable maintenance of all current medication therapy for 3 months, including ARBs for treated groups
- •Exclusion criteria
- •Current therapy with Angiotensin-converting-enzyme (ACE) inhibitor,or Intolerance to Angiotensin II receptor blockers (ARB)
- •Women of child bearing potential
- •Current use of nonsteroidal antiinflammatory drugs or potassium supplementation, treatment with aliskiren, anticoagulation
- •COPD exacerbation requiring treatment within 6 weeks of the screening visit
- •Oral corticosteroid use within 6 weeks of the screening visit
- •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
- •Untreated arterial hypertension (systolic blood pressure >140 mm Hg, diastolic blood pressure > 90 mm Hg)
- •Ability to understand and willingness to sign consent documents
- •Blood pressure less than 100 mm Hg systolic or 70 mm Hg diastolic while standing at the screening visit
- •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
- •History of renal artery stenosis
- •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)
- •History of pulmonary malignancies, and any other malignancies in the last 5 years
- •History of thoracic surgery.
- •Acute pulmonary exacerbation within 6 weeks from the Screening Visit.
- •Subjects with no airflow obstruction by spirometry but with a decrease in diffusing capacity of lung for carbon monoxide(DLco) possibly indicating emphysema.
- •Significant exposure to environmental tobacco smoke or atmospheric or occupational pollutants
- •Urine pregnancy positive test at the Screening Visit.
Exclusion Criteria
- Not provided
Arms & Interventions
Healthy non-smokers
10 healthy non-smokers will receive 50 mg of Losartan for 4 consecutive weeks followed by 100 mg of Losartan for 4 consecutive weeks.
Intervention: Losartan 50 mg (Drug)
Healthy non-smokers
10 healthy non-smokers will receive 50 mg of Losartan for 4 consecutive weeks followed by 100 mg of Losartan for 4 consecutive weeks.
Intervention: Losartan 100 mg (Drug)
Smokers without COPD
10 smokers without COPD will receive 50 mg of Losartan for 4 consecutive weeks followed by 100 mg of Losartan for 4 consecutive weeks.
Intervention: Losartan 50 mg (Drug)
Smokers without COPD
10 smokers without COPD will receive 50 mg of Losartan for 4 consecutive weeks followed by 100 mg of Losartan for 4 consecutive weeks.
Intervention: Losartan 100 mg (Drug)
Ex-smokers with COPD
10 ex-smokers with COPD will receive 50 mg of Losartan for 4 consecutive weeks followed by 100 mg of Losartan for 4 consecutive weeks.
Intervention: Losartan 50 mg (Drug)
Ex-smokers with COPD
10 ex-smokers with COPD will receive 50 mg of Losartan for 4 consecutive weeks followed by 100 mg of Losartan for 4 consecutive weeks.
Intervention: Losartan 100 mg (Drug)
Outcomes
Primary Outcomes
Change in Nasal Potential Difference (NPD).
Time Frame: Baseline, 8 weeks
NPD were assessed from nasal cells collected using sterile cytology brushes.
Secondary Outcomes
- Change in IL-8 Concentrations(Baseline, 8 weeks)
- Percent Change in TGF-ß mRNA Expression(Baseline, 8 weeks)
Investigators
Rafael Calderon Candelario
Assistant Professor
University of Miami