Effect of Losartan on Airway Mucociliary Dysfunction in Patients With COPD and Chronic Bronchitis

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 Overview

• Status: Terminated
• Conditions: COPD; Chronic Bronchitis
• Intervention / Treatment: Drug: Losartan 50 mg; Drug: Losartan 100 mg

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: Losartan 50 mg; 50 mg Losartan taken orally once daily for 4 consecutive weeks.; Other Names: Cozaar; Drug: Losartan 100 mg; 50 mg Losartan taken orally twice daily for 4 consecutive weeks.; Other Names: Cozaar
Experimental: 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.	Drug: Losartan 50 mg; 50 mg Losartan taken orally once daily for 4 consecutive weeks.; Other Names: Cozaar; Drug: Losartan 100 mg; 50 mg Losartan taken orally twice daily for 4 consecutive weeks.; Other Names: Cozaar
Experimental: 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.	Drug: Losartan 50 mg; 50 mg Losartan taken orally once daily for 4 consecutive weeks.; Other Names: Cozaar; Drug: Losartan 100 mg; 50 mg Losartan taken orally twice daily for 4 consecutive weeks.; Other Names: Cozaar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Nasal Potential Difference (NPD).	NPD were assessed from nasal cells collected using sterile cytology brushes.	Baseline, 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in IL-8 Concentrations	Interleukin (IL)-8 concentrations were analyzed from samples on nasal lavage	Baseline, 8 weeks
Percent Change in TGF-ß mRNA Expression	Transforming Growth Factor (TGF)-ß messenger ribonucleic acid (mRNA) expression were analyzed from nasal cells samples.	Baseline, 8 weeks

Collaborators and Investigators

• Sponsor: University of Miami
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Flight Attendant Medical Research Institute
• Investigators: Principal Investigator: Rafael Calderon, MD, University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2016
• Primary Completion (Actual): April 3, 2017
• Study Completion (Actual): April 3, 2017

Study Registration Dates

• First Submitted: January 16, 2015
• First Submitted That Met QC Criteria: April 8, 2015
• First Posted (Estimate): April 14, 2015

Study Record Updates

• Last Update Posted (Actual): August 20, 2020
• Last Update Submitted That Met QC Criteria: August 7, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Bronchial Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Acute Disease; Bronchitis; Bronchitis, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: 20140722; R01HL133240 (U.S. NIH Grant/Contract); R01HL139365 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No