Investigating Mucinase Activity in Airway Disease

Asthma Clinical Trial

— Mucinase  

Official title:

Investigating Mucinase Activity in Airway Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00596232
• Other study ID #: 11-05418
• Secondary ID: 5P01HL107202-03
• Status: Completed
• Phase: N/A
• First received: January 2, 2008
• Last updated: April 28, 2016
• Start date: April 2003
• Est. completion date: April 2016

Study information

• Verified date: April 2016
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to investigate how mucus (phlegm or spit) is broken down once it forms in the airways (bronchial tubes) of people with lung disease. This research study will also examine whether blood groups have an effect on lung function or the type of mucus found in the lung. This study is not designed to be a treatment for asthma, emphysema, cystic fibrosis, or other lung disease. It is designed to help the investigators learn more about the causes of airway disease.

Description:

Accumulation of mucus in the airway involves the process of overproduction and reduced clearance of mucin glycoproteins. To date, little attention has been focused on mechanisms of mucin clearance from the airway. We hypothesize that there is enzymatic degradation of mucins ("mucinase activity") in the airway, which acts to break down mucins and facilitate their clearance. We further hypothesize that glycosidases function as mucinases by removing peripheral monosaccharides from oligosaccharides, including oligosaccharides on mucins. Removal of terminal or capping sugars on mucin side chains may be an important mechanism in mucin degradation and clearance from the lung. If mucinase activity exists in the airway then mucus collected from human subjects should demonstrate evidence of mucin degradation ex vivo, especially at 37º celsius. As part of our protocol we propose to examine changes in airway mucus ex vivo under different experimental conditions. Our primary readout will be measures of sputum rheology, namely viscosity and elasticity. Our consultant for this methodology will be Dr Susan Muller (Chemical Engineering, University of California, Berkeley). In order to conduct experimental studies in this way we will need multiple samples from the same subjects. Thus, up to 10 or more sputum samples per subject will be collected on different days. In addition, we are interested in the biochemical properties of sputum and saliva, specifically the composition of mucin molecules found in these fluids.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 211
• Est. completion date: April 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

Asthma:

1. Male and female subjects aged 18 - 70 years

2. Medical history consistent with asthma

3. PC20 (provocative concentration causing a 20% fall) methacholine = 8 mg/ml for subjects not taking inhaled corticosteroids

4. PC20 methacholine = 16 mg/ml for subjects taking inhaled corticosteroids

5. Ability to provide informed consent

Cystic Fibrosis:

1. Male and female subjects aged 18-55 years

2. Prior diagnosis of cystic fibrosis

3. Ability to provide informed consent

Healthy:

1. Male and female subjects aged 18-70 years

2. No current smoking history

3. No history of asthma or allergic rhinitis

4. FEV1 (forced expiratory volume in 1 second) > 80% predicted

5. Ability to provide informed consent

Exclusion Criteria:

1. Recent heart attack or stroke

2. Known aortic or cerebral aneurysm

3. Uncontrolled hypertension

4. Pregnancy

5. Lactation

6. Lung disease other than asthma,cystic fibrosis, or chronic obstructive pulmonary disease (COPD)/emphysema/chronic bronchitis

7. Upper- or lower-respiratory tract infection 6 weeks prior to study enrollment

8. Significant asthma exacerbation 6 weeks prior to study enrollment

9. Increasing hyposensitization therapy for the past 3 months

Study Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Asthma
• Cystic Fibrosis

Locations

Country	Name	City	State
United States	UCSF Airway Clinical Research Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	rheological measurements (viscosity and elasticity) in sputum.		2-3 years	No

External Links

•   Airway Clinical Research Center website