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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00843817
First Posted: February 13, 2009
Last Update Posted: February 27, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
University Hospital, Tours
  Purpose
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 Intervention Phase
Cystic Fibrosis Drug: Pulmozyme Phase 4

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by University Hospital, Tours:

Primary Outcome Measures:
  • 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 ]

Enrollment: 15
Actual Study Start Date: April 2009
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DRUG
PULMOZYME
Drug: Pulmozyme
Pulmozyme® 2.5mg by inhalation

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00843817


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     History of Changes
Other Study ID Numbers: PHAO08-PD BioDNase
First Submitted: February 12, 2009
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:
Fibrosis
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases