RhDNase and Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum (BioDNase)

• ClinicalTrials.gov Identifier: NCT00843817
• Recruitment Status: Completed
• First Posted: February 13, 2009
• Last Update Posted: February 27, 2017
• Sponsor: University Hospital, Tours
• Information provided by (Responsible Party): University Hospital, Tours

Tracking Information

• First Submitted Date: February 12, 2009
• First Posted Date: February 13, 2009
• Last Update Posted Date: February 27, 2017
• Actual Study Start Date: April 2009
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 12, 2009): The biodistribution of elastase, Protease 3 and cathepsine G in the expectorations will be measured by the management report of these proteases between the freezing fractionand the soluble fraction, before and after rhDNase administration. [ Time Frame: 1 hour ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: RhDNase and Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum
• Official Title: RhDNase Effect on Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum
• Brief Summary: Serine proteases belonging to the elastase family are mainly responsible for lung tissue destruction as observed during cystic fibrosis. But anti-inflammatory therapies based on systemic or aerosolized protease-inhibitors administration, have not given the expected results until now. One reason would be the impaired access of therapeutic inhibitors to their molecular targets. It was recently shown that neutrophils actively secrete neutrophil extracellular traps (NETs) made of DNA that binds cationic proteases among other molecules. NETs together with DNA passively released from dead neutrophils contribute to the viscosity of CF expectorations which explains that rhDNase treatment fluidifies expectorations and improves the patient status. Preliminary experiments in our laboratory have shown that DNA degradation was associated with a significant increase of proteolytic activity in the sputum soluble fraction. However the efficacy of exogenous inhibitors is also improved in these conditions. Using the specific substrates and methodologies that we developed previously to measure cell-surface associated proteolytic activities, we will study the effects of DNase on the activity of individual proteases, their biodistribution in sputum and their regulation by potential therapeutic inhibitors. Enzymatic, immunochemical and microscopic (confocal and scanning) techniques will first be used for ex vivo studies on sputa freshly collected at the adult and paediatric CRCM in Tours, then on sputa from patients before and after administration of aerosolized rhDNase. We hypothesize that a better understanding of the biodistribution of neutrophil serine proteases and especially their binding to DNA will help designing new therapeutic strategies that facilitate inhibitor access to their protease targets.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Cystic Fibrosis

Intervention

Drug: Pulmozyme

Pulmozyme® 2.5mg by inhalation

Study Arms

Experimental: DRUG

PULMOZYME

Intervention: Drug: Pulmozyme

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 23, 2017): 15
• Original Estimated Enrollment (submitted: February 12, 2009): 30
• Actual Study Completion Date: April 2013
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• cystic fibrosis disease
• with rhDNase treatment

Exclusion Criteria:

• Acute push of the bronchopulmonary attack or hospitalization for treatment of the disease during 2 weeks previous
• Exposure to a antibiotherapy or treatment by corticoids

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT00843817
• Other Study ID Numbers: PHAO08-PD BioDNase
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: University Hospital, Tours
• Study Sponsor: University Hospital, Tours
• Collaborators: Not Provided

Investigators

• Principal Investigator: Patrice DIOT, PHD; University Hospital, Tours

• PRS Account: University Hospital, Tours
• Verification Date: February 2017