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Miami, Florida 33136


This is a proof of concept, open label protocol to evaluate the effect of losartan on cigarette smoke-induced lung injury in smokers, ex-smokers with and without chronic obstructive pulmonary disease (COPD), giving 50 mg and subsequently 100 mg losartan for 4 weeks Aim: To test that inhibition of T-cell growth factor (TGF-ß) with losartan in ex-smokers with COPD and active and passive smokers without COPD will lead to an increase chloride conductance through calcium-activated chloride channel (CACC), as measured by nasal potential difference (NPD). Study design: The Investigators will assess the consequences of active and passive smoking and the treatment with losartan on CaCC-mediated chloride conductance in human beings using NPD measurements. NPD is a direct measure of ion transport. It measures CaCC-mediated Cl- secretion and thus serves as an indirect measure of voltage-dependent potassium (BK) channels function. In addition, improvement of NPD measured ion transport was indirectly linked to lung function improvements and clearance in trials with cystic fibrosis patients. Therefore, NPD lends itself as a good surrogate for Mucociliary clearance (MCC), in a proof of concept clinical trial. The investigators will also measure TGF-ß levels in nasal secretions and cells to correlate these with the level of CaCC-mediated Cl- conductance.

Study summary:

Investigator's preliminary data show that TGF-ß1 and cigarette smoke exposure decrease BK activity and cause airway surface liquid (ASL) volume depletion and losartan partially rescues BK channel function leading to increased ASL volume and ciliary beat frequency (CBF) in airway epithelial cells exposed to smoke. Therefore the investigators propose that smoke exposure, via TGF-ß1 production, leads to apical BK channel dysfunction to cause ASL volume depletion and mucociliary dysfunction in smokers and ex-smokers with COPD. Clinically used Angiotensin II Receptor Blockers (ARBs) are known to inhibit TGF-ß signaling and present a "low-hanging-fruit" approach (medication already in clinical use) for intervention in COPD. In a murine model, losartan has previously been shown to attenuate cigarette smoke-induced lung injury and to rescue lung architecture. The long-term goal of this study is evaluate the effect of currently available and clinically useful TGF-ß1 signaling inhibitors (ARBs) on mucociliary function in individuals with smoke-associated airway diseases, such as chronic bronchitis and COPD. To test that hypothesis, subjects with COPD will be given four weeks of 50 mg of losartan daily and consequently an additional four weeks of 100 mg of losartan (divided in two doses of 50 mg twice daily).


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 ACE inhibitor,or Intolerance to 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.



Primary Contact:

Principal Investigator
Rafael Calderon, MD
University of Miami

Backup Contact:


Location Contact:

Miami, Florida 33136
United States

There is no listed contact information for this specific location.

Site Status: N/A

Data Source: ClinicalTrials.gov

Date Processed: November 18, 2019

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