- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00843817
RhDNase and Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum (BioDNase)
February 28, 2022 updated by: University Hospital, Tours
RhDNase Effect on Biodistribution of PMN Serine Proteases in Cystic Fibrosis Sputum
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.
Study Overview
Study Type
Interventional
Enrollment (Actual)
15
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Tours, France
- University Hospital - Tours
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: DRUG
PULMOZYME
|
Pulmozyme® 2.5mg by inhalation
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
1 hour
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Patrice DIOT, PHD, University Hospital, Tours
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 1, 2009
Primary Completion (Actual)
April 1, 2013
Study Completion (Actual)
April 1, 2013
Study Registration Dates
First Submitted
February 12, 2009
First Submitted That Met QC Criteria
February 12, 2009
First Posted (Estimate)
February 13, 2009
Study Record Updates
Last Update Posted (Actual)
March 16, 2022
Last Update Submitted That Met QC Criteria
February 28, 2022
Last Verified
February 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- PHAO08-PD BioDNase
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cystic Fibrosis
-
Hospital de Clinicas de Porto AlegreUnknownCystic Fibrosis | Cystic Fibrosis Pulmonary Exacerbation | Cystic Fibrosis in Children | Cystic Fibrosis With ExacerbationBrazil
-
University of Colorado, DenverCystic Fibrosis FoundationTerminatedCystic Fibrosis-related Diabetes | Cystic Fibrosis Pulmonary Exacerbation | Cystic Fibrosis in ChildrenUnited States
-
Royal College of Surgeons, IrelandThe Hospital for Sick Children; Imperial College London; Erasmus Medical Center; University College Dublin and other collaboratorsActive, not recruitingCystic Fibrosis | Adherence, Medication | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis in Children | Cystic Fibrosis Liver DiseaseUnited Kingdom, Ireland
-
Herlev and Gentofte HospitalCopenhagen University Hospital, DenmarkActive, not recruitingMyocardial Infarction | Heart Diseases | Heart Failure | Stroke | Cystic Fibrosis | Heart Failure, Diastolic | Heart Failure, Systolic | Left Ventricular Dysfunction | Cystic Fibrosis-related Diabetes | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis of Pancreas | Cystic Fibrosis, Pulmonary | Cystic...Denmark
-
The Hospital for Sick ChildrenCanadian Cystic Fibrosis FoundationActive, not recruitingCystic Fibrosis | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis in ChildrenCanada
-
Arrowhead PharmaceuticalsTerminatedCystic Fibrosis, PulmonaryAustralia, New Zealand
-
AzurRx SASCompletedCystic Fibrosis | Cystic Fibrosis Gastrointestinal Disease | Cystic Fibrosis of PancreasTurkey, Hungary
-
Dartmouth-Hitchcock Medical CenterTrustees of Dartmouth CollegeWithdrawnCystic Fibrosis-related Diabetes | Cystic Fibrosis Liver Disease | CF - Cystic FibrosisUnited States
-
University Hospital, BordeauxCompleted
-
University of PortsmouthUniversity Hospital Southampton NHS Foundation Trust; Loughborough University; Queen Alexandra HospitalTerminated
Clinical Trials on Pulmozyme
-
Acibadem UniversityThe Scientific and Technological Research Council of TurkeyUnknown
-
University of JenaPD Dr. Joachim Riethmöller, Tübingen; PD Dr. Assen Koitschev, Tübingen; Dr. Gerlind...CompletedCystic Fibrosis | Chronic RhinosinusitisGermany
-
Northwell HealthGenentech, Inc.Completed
-
University of Medicine and Dentistry of New JerseyCompletedAtelectasis | Ventilation, MechanicalUnited States
-
Genentech, Inc.TerminatedCystic FibrosisUnited States
-
Genentech, Inc.Completed
-
McGill University Health Centre/Research Institute...Hoffmann-La Roche; Hamilton Health Sciences Corporation; Exactis InnovationCompletedCOVID-19 InfectionCanada
-
Boston Children's HospitalBrigham and Women's Hospital; South Shore HospitalRecruiting
-
Genentech, Inc.Terminated
-
University of Colorado, DenverGenentech, Inc.CompletedOtitis MediaUnited States