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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: Pulmozyme	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: RhDNase Effect on Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum
• Actual Study Start Date: April 2009
• Actual Primary Completion Date: April 2013
• Actual Study Completion Date: April 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: DRUG; PULMOZYME	Drug: Pulmozyme; Pulmozyme® 2.5mg by inhalation

Outcome Measures

Primary Outcome Measures :

1. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

France

University Hospital - Tours

Tours, France

Sponsors and Collaborators

University Hospital, Tours

Investigators

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

More Information

• Responsible Party: University Hospital, Tours
• ClinicalTrials.gov Identifier: NCT00843817
• Other Study ID Numbers: PHAO08-PD BioDNase
• First Posted: February 13, 2009
• Last Update Posted: February 27, 2017
• Last Verified: February 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by University Hospital, Tours:

cystic fibrosis

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases