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

• Sponsor: University of Miami (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02416102
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), Flight Attendant Medical Research Institute (Other)
• Enrollment: 31
• Location: 1
• Arms: 3
• Actual Duration (Months): 12.1
• Patients Per Site Per Month: 2.6

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
COPD; Chronic Bronchitis	Drug: Losartan 50 mg; Drug: Losartan 100 mg	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Effect of Losartan on Airway Mucociliary Dysfunction in Patients With COPD and Chronic Bronchitis
• Actual Study Start Date: Mar 31, 2016
• Actual Primary Completion Date: Apr 3, 2017
• Actual Study Completion Date: Apr 3, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Nasal Potential Difference (NPD). [Baseline, 8 weeks]

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

Secondary Outcome Measures

1. Change in IL-8 Concentrations [Baseline, 8 weeks]

   Interleukin (IL)-8 concentrations were analyzed from samples on nasal lavage

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami	Miami	Florida	United States	33136

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Rafael Calderon, MD, University of Miami

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 1, 2019

More Information

Publications

None provided.

• Responsible Party: Rafael Calderon Candelario, Assistant Professor, University of Miami
• ClinicalTrials.gov Identifier: NCT02416102
• Other Study ID Numbers: 20140722; R01HL133240; R01HL139365
• First Posted: Apr 14, 2015
• Last Update Posted: Aug 20, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Bronchitis; Bronchitis, Chronic; Acute Disease; Losartan

Study Results

Participant Flow

Arm/Group Title	Healthy Non-smokers	Smokers Without COPD	Ex-smokers With COPD
Arm/Group Description	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 once daily (QD) for 4 weeks losartan 100 mg: 50 mg twice daily (BID) for 4 weeks	10 smokers without Chronic Obstructive Pulmonary Disease (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	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
Period Title: Overall Study
STARTED	16	15	0
COMPLETED	7	7	0
NOT COMPLETED	9	8	0

Baseline Characteristics

Arm/Group Title	Healthy Non-smokers	Smokers Without COPD	Ex-smokers With COPD	Total
Arm/Group Description	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	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	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	Total of all reporting groups
Overall Participants	16	15	0	31
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 NaN	0 0%
Between 18 and 65 years	15 93.8%	15 100%	0 NaN	30 96.8%
>=65 years	1 6.3%	0 0%	0 NaN	1 3.2%
Sex: Female, Male (Count of Participants)
Female	13 81.3%	8 53.3%	0 NaN	21 67.7%
Male	3 18.8%	7 46.7%	0 NaN	10 32.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 81.3%	13 86.7%	0 NaN	26 83.9%
Not Hispanic or Latino	3 18.8%	2 13.3%	0 NaN	5 16.1%
Unknown or Not Reported	0 0%	0 0%	0 NaN	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 NaN	0 0%
Asian	0 0%	0 0%	0 NaN	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 NaN	0 0%
Black or African American	0 0%	2 13.3%	0 NaN	2 6.5%
White	13 81.3%	9 60%	0 NaN	22 71%
More than one race	1 6.3%	1 6.7%	0 NaN	2 6.5%
Unknown or Not Reported	2 12.5%	3 20%	0 NaN	5 16.1%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Nasal sample data for all participants were not available as the readings were uninterpretable and not further analyzed.

Arm/Group Title	Healthy Non-smokers	Smokers Without COPD	Ex-smokers With COPD
Arm/Group Description	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	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	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
Measure Participants	0	0	0

2. Secondary Outcome

Title	Change in IL-8 Concentrations
Description	Interleukin (IL)-8 concentrations were analyzed from samples on nasal lavage
Time Frame	Baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Non-smokers	Smokers Without COPD	Ex-smokers With COPD
Arm/Group Description	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	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	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
Measure Participants	5	5	0
Mean (Standard Deviation) [pg/mL]	2867 (1685)	4676 (1948)

3. Secondary Outcome

Title	Percent Change in TGF-ß mRNA Expression
Description	Transforming Growth Factor (TGF)-ß messenger ribonucleic acid (mRNA) expression were analyzed from nasal cells samples.
Time Frame	Baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Healthy Non-smokers	Smokers Without COPD	Ex-smokers With COPD
Arm/Group Description	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	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	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
Measure Participants	5	5	0
Mean (Standard Deviation) [percentage change in mRNA expression]	-51 (31)	-23 (70)

Adverse Events

Time Frame	8 Weeks
Adverse Event Reporting Description	Only treatment-emergent Adverse Events will be reported as per treating physician discretion.
Arm/Group Title	Healthy Non-smokers		Smokers Without COPD		Ex-smokers With COPD
Arm/Group Description	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		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		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
All Cause Mortality
	Healthy Non-smokers		Smokers Without COPD		Ex-smokers With COPD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/15 (0%)		0/0 (NaN)
Serious Adverse Events
	Healthy Non-smokers		Smokers Without COPD		Ex-smokers With COPD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/15 (0%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Healthy Non-smokers		Smokers Without COPD		Ex-smokers With COPD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/15 (0%)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.