Interest of Gentamicin-induced Readthrough in Cystic Fibrosis Patients
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ClinicalTrials.gov Identifier: NCT00376428 |
Recruitment Status :
Terminated
First Posted : September 14, 2006
Last Update Posted : February 25, 2015
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Cystic Fibrosis | Drug: Gentamicin | Phase 2 |
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.
Study Type : | Interventional (Clinical Trial) |
Enrollment : | 20 participants |
Allocation: | Non-Randomized |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Application of Functional Electrophysiological Tests to Evaluate Pharmacological Treatments in Patients With Cystic Fibrosis |
Study Start Date : | January 2003 |
Study Completion Date : | June 2005 |

- CFTR-dependant chlorate secretion
- CFTR expression in nasal cells
- Clinical beneficial effects

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Ages Eligible for Study: | Child, Adult, Older Adult |
Sexes Eligible for Study: | All |
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

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): NCT00376428
France | |
Necker-Enfants malades | |
Paris, France, 75015 |
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 |
ClinicalTrials.gov Identifier: | NCT00376428 |
Other Study ID Numbers: |
02-03-10 |
First Posted: | September 14, 2006 Key Record Dates |
Last Update Posted: | February 25, 2015 |
Last Verified: | September 2006 |
Cystic Fibrosis Transmembrane Conductance Regulator Premature termination codon Gentamicin-induced readthrough |
Cystic Fibrosis Fibrosis Pathologic Processes Pancreatic Diseases Digestive System Diseases Lung Diseases Respiratory Tract Diseases Genetic Diseases, Inborn |
Infant, Newborn, Diseases Gentamicins Anti-Bacterial Agents Anti-Infective Agents Protein Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |