RhDNase and Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum

NCT00843817 | Completed Phase 4

• 1 other identifier: PHAO08-PD BioDNase
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis

Keywords

cystic fibrosis

Outcome Measures

Primary Outcomes (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.

  1 hour

Study Arms (1)

DRUG

EXPERIMENTAL

PULMOZYME

Drug: Pulmozyme

Interventions

Pulmozyme DRUG

Pulmozyme® 2.5mg by inhalation

DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• cystic fibrosis disease
• with rhDNase treatment

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (1)

University Hospital - Tours

Tours, France

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

dornase alfa

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Patrice DIOT, PHD

  University Hospital, Tours

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2009
• First Posted: February 13, 2009
• Study Start: April 1, 2009
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: March 16, 2022

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)