Clinical trial NCT01792271: Sustained Effects of Hypertonic Saline on Mucociliary Clearance in Subjects With Chronic Bronchitis
Official title: Novel Therapies for Muco-Obstructive Lung Diseases: Sustained Effects of Hypertonic Saline on Mucociliary Clearance and Clinical Tolerability in Subjects With Chronic Bronchitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Obstructive Pulmonary Disease
COPD
Chronic Bronchitis
Keywords: COPD
Chronic Bronchitis
Hypertonic Saline
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2013-02-15
Enrollment: 25
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to examine the effects of two weeks of daily dosing of inhaled salt water mist (hypertonic saline - HS) on actual measurements of mucociliary and cough clearance in patients with the chronic bronchitis type of Chronic Obstructive Pulmonary Disease (COPD.

Defective mucociliary clearance (MCC) is central to the development and/or worsening of several kinds of lung diseases, including COPD/chronic bronchitis (CB), cystic fibrosis (CF), and bronchiectasis. In each case, defective MCC leads to the development of lung infections and damage to the airways from ongoing inflammation caused by a person's inability to clear mucus from the lungs.

The investigators' previous studies have shown that the administration of inhaled HS (hypertonic saline) not only acutely accelerates MCC in CF, but also that repetitive use "resets" the baseline rate of MCC within 2 weeks. It is likely that the sustained effect of HS on MCC was responsible for the \~60% reduction in the frequency of pulmonary disease exacerbations, reduced antibiotic use and improved lung function in a long-term study of HS in CF volunteers. As a result, HS has now become a standard therapy for CF lung disease and its success raises optimism that similar benefits might occur in patients with CB.

In this study the investigators will use mildly radioactive particles, technetium bound to sulfur colloid, to measure and compare the sustained effects on mucus clearance of two weeks of daily dosing of 7% hypertonic saline versus a low salt control treatment for subjects with CB. We will also be collecting sputum and breath condensation to analyze for protein and inflammatory changes that might occur with exacerbations.

Our long term goals are to improve our understanding of MCC in health and disease and to develop better therapies that support and/or restore MCC in patients with these diseases to reduce lung infections.


Eligibility criteria: Inclusion Criteria:

Volunteers who meet all of the following criteria will be eligible for study participation:

1. Age 40-80 years, inclusive
2. Non-pregnant subjects must be either not sexually active, post-menopausal, surgically sterilized, or agree to use an appropriate "double barrier" method (such as diaphragm and condom), or must currently be using a prescribed transdermal, injection, implant, or oral contraceptive during study participation.
3. Forced expiratory volume in 1 second (FEV1) of 35-80% of predicted, inclusive, and FEV1/forced vital capacity (FVC) \< 70%
4. Produces mucus at least 2 days per week, on average
5. History of smoking (≥ 10 pack years) -

Exclusion Criteria:

Volunteers will be excluded from the study if they meet any of the following criteria:

1. Uses oxygen continuously during daytime hours (nighttime use OK)
2. Requires \> 10mg per day of prednisone (or equivalent corticosteroid dose) chronically
3. Concomitant presence of congestive heart failure, active coronary syndromes, or other disease that in the opinion of the investigator would increase the risk resulting from participation
4. Recent change in respiratory medications, including acute antibiotic or systemic corticosteroid interventions within the last 4 weeks
5. History of intolerance or hypersensitivity to hypertonic saline or short acting inhaled beta agonist
6. Significant broncho reactivity by examination or pulmonary function testing (PFT), that in the opinion of the investigator would increase the risk of HS use
7. Radiation exposure within the 12 months prior to study participation that would cause them to exceed Federal Regulations by participating in this study
8. Subjects with a positive pregnancy test
9. Subjects who, in the opinion of the Principal Investigator, should not participate in the study

Subjects may be temporarily excluded from screening should they experience a respiratory tract infection that requires treatment with antibiotics and/or steroids. They may become eligible for screening four weeks after completing their treatment providing their symptoms have resolved.

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Primary outcomes:
measure: Measure and compare the sustained effects on mucus clearance of two weeks of daily dosing of hypertonic saline versus a low salt control treatment for subjects with CB.
timeFrame: Approximately 11 weeks
Secondary outcomes:
measure: We will also be collecting sputum and breath condensation to analyze for protein and inflammatory changes that might occur with exacerbations.
timeFrame: Within 2 years after all data collection has ended
Other outcomes:
measure: Changes in lung function testing (spirometry)
timeFrame: within 11 weeks of enrollment of subjects
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Ashley G Henderson, MD
role: PRINCIPAL_INVESTIGATOR
References: