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Peripheral targeting of inhaled rhDNase in stable CF patients.

Completed
Conditions
Cystic Fibrosis, rhDNase (Pulmozyme), inhalation, airways.
Registration Number
NL-OMON23855
Lead Sponsor
Investigator initiated study.Initiator: Harm Tiddens, M.D. PhD.ErasmusMC - Sophia Children's Hospital
Brief Summary

Earlier publications have shown that: - patients develop chronic airway infection and inflammation which start early in life [1. Dakin, C.J., et al., Inflammation, infection, and pulmonary function in infants and young children with cystic fibrosis. Am J Respir Crit Care Med, 2002. 165(7): p. 904-10. 2. Armstrong, D.S., et al., Lower airway inflammation in infants and young children with cystic fibrosis. Am J Respir Crit Care Med, 1997. 156(4 Pt 1): p. 1197-204. 3. Nixon, G.M., et al., Early airway infection, inflammation, and lung function in cystic fibrosis. Arch Dis Child, 2002. 87(4): p. 306-11]. And that: - Predominantly the peripheral airways are damaged and filled with sputum in CF [Tiddens, H.A., et al., Cartilaginous airway wall dimensions and airway resistance in cystic fibrosis lungs. Eur Respir J, 2000. 15(4): p. 735-42]. Therefore we hypothesize that rhDNase targeted to the peripheral airways can improve lung function in children with CF.

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
Not specified
Target Recruitment
50
Inclusion Criteria

1. Age between 6 and 18 years old;
2. Diagnosis of CF confirmed by sweat-test and/or DNA analysis and/or electro physiology testing (nasal potential difference measurement);
3. Routine treatment with rhDNase once daily, started at least one month before enrolment in the study;
4. Stable condition, in this study defined as: no i.v antibiotics (hospital or at home) in the previous month and constant medication regime during the previous 2 weeks (for example: no additional oral antibiotics course, no newly started inhaled or systemic corticosteroids etc).
5. Ability to perform lung function tests (assessed by trained lung function technician);
6. Lung function: FVC > 40% predicted;
7. Signed written informed consent.

Exclusion Criteria

1. Inability to follow instructions of the investigator;
2. Inability to inhale rhDNase;
3. Clinical condition not stable, as assessed by the patient’s paediatrician;
4. Concomitant medical conditions that effect inhaled treatment (e.g. cleft palate, severe malacia);
5. Current respiratory tract infection;
6. Pulmonary complications that might put the patient at risk to participate in the study;
7. Neuromuscular disease;
8. Poor compliance with treatment as assessed by the patient’s paediatrician;
9. Active ABPA (allergic bronchopulmonary aspergillosis) defined as an oral course of prednisone for ABPA within the last three months.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Primary endpoint will be the change in FEF75 as a result of treatment. FEF75 is the most suitable endpoint since it is sensitive to peripheral airways obstruction.
Secondary Outcome Measures
NameTimeMethod
Secondary endpoints will include: <br>1. Lung clearance index (LCI) measurements as assessed by multiple breath washout; <br>2. Other values obtained in the flow volume curve: MMEF25-75, FEV1, FVC.<br>3. Other study parameters, such as use of antibiotics and number of exacerbations (if applicable).<br>
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