The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis - Full Text View

Purpose

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

Condition	Intervention	Phase
Cystic Fibrosis	Drug: rhDNAse Other: Placebo	Phase IV

Genetics Home Reference related topics:

cystic fibrosis

MedlinePlus related topics:

Cystic Fibrosis

ChemIDplus related topics:

Dornase alfa

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Efficacy Study

Official Title:	Randomized, Placebo-Controlled Trial on the Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis

Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:

The change in LCI from baseline to end of treatment in rhDnase treated patients versus patients receiving placebo [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in FEV1 % predicted [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ] [ Designated as safety issue: No ]
Change in FVC (in litres) [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ] [ Designated as safety issue: No ]
Change in FVC % predicted [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ] [ Designated as safety issue: No ]
Change in FEF25-75 (liters/sec) [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ] [ Designated as safety issue: No ]
Change in FEF25-75 % predicted [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ] [ Designated as safety issue: No ]
Change in exhaled nitric oxide concentrations [ Time Frame: The duration of the patient's involvement in the study (approximately 3 months) ] [ Designated as safety issue: No ]
Incidence of adverse events and serious adverse events [ Time Frame: Duration of the study (approximately 1 year) ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	19
Study Start Date:	January 2008
Estimated Study Completion Date:	July 2009
Estimated Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1 This arm will receive the active treatment for 28 days, followed by a 28 day washout period and then the placebo treatment for 28 days.	Drug: rhDNAse 2.5 mg rhDNase will be dispensed in 2.5 ml vials and administered once a day for 28 days. Treatment will be administered by inhalation. Other: Placebo 2.5 mg of the placebo will be dispensed in 2.5 ml vials and administered once a day over 28 days. Treatment will be administered by inhalation.
2 This arm will receive the placebo treatment for 28 days, followed by a 28 day washout period and then the active treatment for 28 days.	Drug: rhDNAse 2.5 mg rhDNase will be dispensed in 2.5 ml vials and administered once a day for 28 days. Treatment will be administered by inhalation. Other: Placebo 2.5 mg of the placebo will be dispensed in 2.5 ml vials and administered once a day over 28 days. Treatment will be administered by inhalation.

Detailed 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.

Eligibility

Ages Eligible for Study:	6 Years to 18 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00557089

Contacts


Contact: Felix Ratjen, MD	416-813-6167	felix.ratjen@sickkids.ca

Locations


Canada, Ontario
	The Hospital for Sick Children	Recruiting
	Toronto, Ontario, Canada, M5G 1X8
	Contact: Felix Ratjen, MD 416 813 6167 felix.ratjen@sickkids.ca
	Principal Investigator: Felix Ratjen, MD
	Sub-Investigator: Padmaja Subbarao, MD

Sponsors and Collaborators

The Hospital for Sick Children

Investigators


Principal Investigator:	Felix Ratjen, MD	The Hospital for Sick Children, Toronto Canada

More Information

Responsible Party:	The Hospital for Sick Children ( Felix Ratjen/Principal Investigator )
Study ID Numbers:	1000010903
First Received:	November 9, 2007
Last Updated:	May 22, 2008
ClinicalTrials.gov Identifier:	NCT00557089
Health Authority:	Canada: Ethics Review Committee

Keywords provided by The Hospital for Sick Children:

Pediatrics

Cystic Fibrosis

Lung Clearance Index

rhDNAse

Study placed in the following topic categories:

Digestive System Diseases

Genetic Diseases, Inborn

Respiratory Tract Diseases

Cystic Fibrosis

Fibrosis

Lung Diseases

Infant, Newborn, Diseases

Pancreatic Diseases

Cystic fibrosis

Additional relevant MeSH terms:

Pathologic Processes

ClinicalTrials.gov processed this record on September 22, 2008

Sponsored by:	The Hospital for Sick Children
Information provided by:	The Hospital for Sick Children
ClinicalTrials.gov Identifier:	NCT00557089