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

NCT02416102 | Terminated Phase 4 Results FDA Drug

• 3 other identifiers: 20140722R01HL133240R01HL139365
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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).

Conditions

COPD; Chronic Bronchitis

Outcome Measures

Primary Outcomes (1)

• Change in Nasal Potential Difference (NPD).

  NPD were assessed from nasal cells collected using sterile cytology brushes.

  Baseline, 8 weeks

Secondary Outcomes (2)

• Change in IL-8 Concentrations

  Baseline, 8 weeks

• Percent Change in TGF-ß mRNA Expression

  Baseline, 8 weeks

Study Arms (3)

Healthy non-smokers

ACTIVE COMPARATOR

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; Drug: Losartan 100 mg

Smokers without COPD

EXPERIMENTAL

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; Drug: Losartan 100 mg

Ex-smokers with COPD

EXPERIMENTAL

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; Drug: Losartan 100 mg

Interventions

Losartan 50 mg DRUG

50 mg Losartan taken orally once daily for 4 consecutive weeks.

Also known as: Cozaar

Ex-smokers with COPD; Healthy non-smokers; Smokers without COPD

Losartan 100 mg DRUG

50 mg Losartan taken orally twice daily for 4 consecutive weeks.

Also known as: Cozaar

Ex-smokers with COPD; Healthy non-smokers; Smokers without COPD

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Miami: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Flight Attendant Medical Research Institute: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Bronchitis, Chronic

Interventions

Losartan

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchitis; Respiratory Tract Infections; Infections; Bronchial Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Results Point of Contact

• Title: Matthias Salathe, MD
• Organization: University of Miami

msalathe@kumc.edu

913-588-6000

Study Officials

• Rafael Calderon, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 16, 2015
• First Posted: April 14, 2015
• Study Start: March 31, 2016
• Primary Completion: April 3, 2017
• Study Completion: April 3, 2017
• Last Updated: August 20, 2020
• Results First Posted: August 20, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)