Ignite Creation Date:
2024-05-05 @ 5:03 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00376428
Status:
TERMINATED
Last Update Posted:
2015-02-25
First Post:
2006-09-13
Brief Title:
Interest of Gentamicin-induced Readthrough in Cystic Fibrosis Patients
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Application of Functional Electrophysiological Tests to Evaluate Pharmacological Treatments in Patients With Cystic Fibrosis
Status:
TERMINATED
Status Verified Date:
2006-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
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 mgkg 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 n4 and those without stop mutations n5
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
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 mgkg 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 n4 and those without stop mutations n5
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None