Cystic Fibrosis
Conditions
Brief summary
The purpose of this study is to characterize the rheological properties of cystic fibrosis (CF) and healthy sputum and to examine the effects of mucoactive agents on the rheology of CF and healthy sputum. By collaborating with Genentech, the investigators (scientists at UCSF) plan to incorporate the latest scientific findings into our work to discover and develop new treatments for CF.
Detailed description
There are two major mechanisms for mucus clearance in the airway, both of which are dependent upon optimal mucus viscosity and elasticity. These mechanisms are severely impaired in cystic fibrosis. The physical properties of sputum can be measured using rheological methods, enabling comparison between mucus in health and in disease. Therapies which enhance mucus clearance from the airway and decrease the volume of airway secretions are collectively called mucoactive agents. Therapies which specifically disrupt innate mucus architecture by breaking intermolecular entanglements and bonds are called mucolytic agents. Mucolytic drugs can be considered in three general categories: classic mucolytics (n-acetylcysteine), peptide mucolytics (Pulmozyme®), and non-destructive mucolytics (hypertonic saline). Using state-of-the-art rheological methods, we can characterize the physical properties of CF mucus and measure the rheologic effects of mucoactive drugs more accurately and reproducibly than what has been previously done in the literature. In this way, we will determine which of the current mucoactive agents are most effective in normalizing sputum rheology in CF, and we will gain important insights about the limitations of current mucoactive drugs.
Interventions
None listed
Sponsors
Genentech, Inc.
University of California, San Francisco
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy control subjects: * Age 18-65 * No history of lung disease or cardiac disease * Cystic fibrosis subjects: * Age 18-65 * Diagnosis of CF - sweat chloride values \> 60 mM on pilocarpine iontophoresis sweat tests and/or 2 allelic CF-producing mutations by genetic analysis
Exclusion criteria
* Use of recreational drugs within 1 year prior to enrollment * Use of tobacco within 1 year prior to enrollment, or \> 10 pack-year tobacco history * Upper respiratory tract infection in the 4 weeks prior to enrollment in the study * Current use of antihistamines to treat allergies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Shear Rheology | Cross-sectional | Baseline measure of sputum shear rheology |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cystic Fibrosis Individuals who have been diagnosed with cystic fibrosis. | 15 |
| Healthy Individuals who do not have cystic fibrosis and who do not have any other lung conditions | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not meet eligibility criteria | 2 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Cystic Fibrosis | Healthy | Total |
|---|---|---|---|
| Age, Continuous | 36.6 years STANDARD_DEVIATION 12.8 | 41.9 years STANDARD_DEVIATION 10.8 | 38.8 years STANDARD_DEVIATION 11.9 |
| Region of Enrollment United States | 15 participants | 15 participants | 30 participants |
| Sex: Female, Male Female | 4 Participants | 9 Participants | 13 Participants |
| Sex: Female, Male Male | 11 Participants | 6 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Shear Rheology
Baseline measure of sputum shear rheology
Time frame: Cross-sectional
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cystic Fibrosis | Shear Rheology | 6.0 Pascal | Standard Error 2 |
| Healthy | Shear Rheology | 1.8 Pascal | Standard Error 0.2 |