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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2009 by University Hospital, Tours.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by:
University Hospital, Tours
ClinicalTrials.gov Identifier:
NCT00843817
First received: February 12, 2009
Last updated: NA
Last verified: February 2009
History: No changes posted
  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: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Pulmozyme
    Pulmozyme® 2.5mg by inhalation
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00843817

Contacts
Contact: Patrice DIOT, PHD diot@med.univ-tours.fr

Locations
France
University Hospital - Tours Not yet recruiting
Tours, France
Contact: Patrice DIOT, PHD       diot@med.univ-tours.fr   
Contact: Pascaline Rameau       rameau@med.univ-tours.fr   
Principal Investigator: Patrice DIOT, PHD         
Sub-Investigator: Francoise Varaigne, MD         
Sponsors and Collaborators
University Hospital, Tours
Investigators
Principal Investigator: Patrice DIOT, PHD University Hospital, Tours
  More Information

No publications provided

Responsible Party: Jocelyne Marlière, University Hospital, Tours
ClinicalTrials.gov Identifier: NCT00843817     History of Changes
Other Study ID Numbers: PHAO08-PD BioDNase
Study First Received: February 12, 2009
Last Updated: February 12, 2009
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Tours:
cystic fibrosis

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 29, 2014