The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis

The Hospital for Sick Children

Status and phase

Completed

Phase 4

Conditions

Cystic Fibrosis

Treatments

Other: Placebo

Drug: rhDNAse

Study type

Interventional

Funder types

Other

Identifiers

NCT00557089

1000010903

Details and patient eligibility

About

This study will assess whether rhDNase treatment improves ventilation inhomogeneity as assessed by lung clearance index (LCI) in patients with cystic fibrosis (CF).

Full description

Life expectancy in CF patients has greatly increased due to improved clinical care. While this is certainly beneficial to CF patients, it has made it more difficult to assess the effect of therapeutic interventions. Currently, FEV1 remains the primary outcome parameter for most clinical trials, but many CF patients have normal pulmonary function and the annual rate of decline is now less than 2 %. Therefore, additional parameters are needed that are more sensitive to define abnormalities in CF patients and that can be used in therapeutic trials.

Gas mixing techniques have been shown to be sensitive parameters to define abnormalities in patients with cystic fibrosis, but it is unclear how useful this technique is to detect changes after a therapeutic intervention. Abnormalities in gas clearance from the lung are largely due to retention of inhaled gases due to mucous obstruction in the lower airways and can be assessed with the lung clearance index (LCI). Interventions that improve mucous accumulation are expected to improve lung clearance as assessed by this technique. RhDNase has been demonstrated to improve lung function and reduce pulmonary exacerbations in patients with cystic fibrosis due to improved mucus clearance.

Lung clearance index (LCI) has been shown to be more sensitive than spirometry in detecting abnormalities in CF patients. Clear cut-offs have been found which can differentiate normal patients from even newly diagnosed CF patients. However, little is known about how LCI may change with treatment.

Enrollment

17 patients

Sex

All

Ages

6 to 18 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Diagnosis of CF as defined by clinical features of CF and a documented sweat chloride > 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease causing mutations
Informed consent and verbal assent (as appropriate) has been provided by the subject's parent or legal guardian and the subject
6-18 years of age at enrolment
Able to perform reproducible spirometry
Clinically stable at enrolment
Ability to comply with medication use, study visits and study procedures as judged by the site investigator
FEV1 % predicted > 70 % as calculated by the Wang reference equations

Exclusion criteria

Respiratory culture positive for:
- NTM within past year or AFB positive at screening (sputum only)
- B. cepacia complex within past year or at screening
Use of intravenous antibiotics or oral quinolones within 14 days of screening
Investigational drug use within 30 days of screening
History of alcohol, illicit drug or medication abuse within 1 year of screening
Other major organ dysfunction excluding pancreatic dysfunction
History of lung transplantation or currently on lung transplant list
Physical findings at screening that would compromise the safety of the participant or the quality of the study data