Interest of Gentamicin-induced Readthrough in Cystic Fibrosis Patients

This study has been terminated.
Information provided by:
Assistance Publique - Hôpitaux de Paris Identifier:
First received: September 13, 2006
Last updated: February 24, 2015
Last verified: September 2006
Suppression of stop mutations in the CFTR gene with parenteral gentamicin can be predicted in vitro and is associated with clinical benefit and significant modification of the CFTR-mediated chloride transport in nasal and sweat gland epithelium.

Condition Intervention Phase
Cystic Fibrosis
Drug: Gentamicin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Application of Functional Electrophysiological Tests to Evaluate Pharmacological Treatments in Patients With Cystic Fibrosis

Resource links provided by NLM:

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • CFTR-dependant chlorate secretion

Secondary Outcome Measures:
  • CFTR expression in nasal cells
  • Clinical beneficial effects

Estimated Enrollment: 20
Study Start Date: January 2003
Estimated Study Completion Date: June 2005
Detailed Description:

Background: This study was conducted to determine whether intravenous gentamicin can suppress stop codons in cystic fibrosis (CF) patients and, if so, whether it has any clinical benefits.

Methods: We first used a dual gene reporter system to determine the gentamicin-induced readthrough level of the most frequent CFTR stop mutations in the French population. We next investigated readthrough efficiency in response to 10 mg/kg once daily intravenous gentamicin perfusions in patients with stop mutations and in a control group of patients without stop mutations. Respiratory function, sweat chloride concentration, nasal potential difference (NPD) and CFTR expression in nasal epithelial cells were measured at baseline and after 15 days of treatment.

Results: After in vitro gentamicin incubation, the readthrough efficiency for the Y122X mutation was at least five times higher than that for G542X, R1162X, and W1282X. In six of the nine patients with the Y122X mutation, CFTR immunodetection showed protein expression at the membrane of the nasal ciliated cells and the CFTR-dependent chloride secretion in their NPD measurements increased significantly. Respiratory status also improved in these patients, irrespective of the gentamicin sensitivity of the germs present in the sputum. Mean sweat chloride concentration decreased significantly and normalized in two patients. These measurements did not change in the Y122X patients with no protein expression, in patients with the other stop mutations investigated in vitro (n=4) and those without stop mutations (n=5).

Conclusion: Suppression of stop mutations in the CFTR gene with parenteral gentamicin can be predicted in vitro and is associated with clinical benefit and significant modification of the CFTR-mediated chloride transport in nasal and sweat gland epithelium.


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • cystic fibrosis with CFTR codon stop mutations

Exclusion Criteria:

  • Rhinitis
  • nasal polyposis
  • passive or active smoking
  • modification of basal treatments within the previous month
  • treatments with aminoglycosides within three previous months
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Please refer to this study by its identifier: NCT00376428

Necker-Enfants malades
Paris, France, 75015
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Study Director: Aleksander Edelman, PhD Institut National de la Santé Et de la Recherche Médicale, France
Principal Investigator: Isabelle Sermet, MD; PhD Assistance Publique - Hôpitaux de Paris
  More Information Identifier: NCT00376428     History of Changes
Other Study ID Numbers: 02-03-10 
Study First Received: September 13, 2006
Last Updated: February 24, 2015
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Cystic Fibrosis Transmembrane Conductance Regulator
Premature termination codon
Gentamicin-induced readthrough

Additional relevant MeSH terms:
Cystic Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Synthesis Inhibitors
Therapeutic Uses processed this record on May 01, 2016