Interest of Gentamicin-induced Readthrough in Cystic Fibrosis Patients

Status Terminated

Clinical Trial 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.

Clinical Trial 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. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

Clinical Trial Details

NCT number	NCT00376428
Study type	Interventional
Source	Assistance Publique - Hôpitaux de Paris
Contact
Status	Terminated
Phase	Phase 2
Start date	January 2003
Completion date	June 2005

View Details

See also
Status	Clinical Trial	Phase
Completed	`NCT04696198` - Thoracic Mobility in Cystic Fibrosis Care	N/A
Completed	`NCT00803205` - Study of Ataluren (PTC124™) in Cystic Fibrosis	Phase 3
Terminated	`NCT04921332` - Bright Light Therapy for Depression Symptoms in Adults With Cystic Fibrosis (CF) and COPD	N/A
Completed	`NCT03601637` - Safety and Pharmacokinetic Study of Lumacaftor/Ivacaftor in Participants 1 to Less Than 2 Years of Age With Cystic Fibrosis, Homozygous for F508del	Phase 3
Terminated	`NCT02769637` - Effect of Acid Blockade on Microbiota and Inflammation in Cystic Fibrosis (CF)
Recruiting	`NCT06030206` - Lung Transplant READY CF 2: A Multi-site RCT	N/A
Recruiting	`NCT06012084` - The Development and Evaluation of iCF-PWR for Healthy Siblings of Individuals With Cystic Fibrosis	N/A
Recruiting	`NCT06032273` - Lung Transplant READY CF 2: CARING CF Ancillary RCT	N/A
Recruiting	`NCT06088485` - The Effect of Bone Mineral Density in Patients With Adult Cystic Fibrosis
Recruiting	`NCT05392855` - Symptom Based Performance of Airway Clearance After Starting Highly Effective Modulators for Cystic Fibrosis (SPACE-CF)	N/A
Recruiting	`NCT04056702` - Impact of Triple Combination CFTR Therapy on Sinus Disease.
Recruiting	`NCT04039087` - Sildenafil Exercise: Role of PDE5 Inhibition	Phase 2/Phase 3
Completed	`NCT04038710` - Clinical Outcomes of Triple Combination Therapy in Severe Cystic Fibrosis Disease.
Completed	`NCT04058548` - Clinical Utility of the 1-minute Sit to Stand Test as a Measure of Submaximal Exercise Tolerance in Patients With Cystic Fibrosis During Acute Pulmonary Exacerbation	N/A
Completed	`NCT03637504` - Feasibility of a Mobile Medication Plan Application in CF Patient Care	N/A
Recruiting	`NCT03506061` - Trikafta in Cystic Fibrosis Patients	Phase 2
Completed	`NCT03566550` - Gut Imaging for Function & Transit in Cystic Fibrosis Study 1
Recruiting	`NCT04828382` - Prospective Study of Pregnancy in Women With Cystic Fibrosis
Completed	`NCT04568980` - Assessment of Contraceptive Safety and Effectiveness in Cystic Fibrosis
Recruiting	`NCT04010253` - Impact of Bronchial Drainage Technique by the Medical Device Simeox® on Respiratory Function and Symptoms in Adult Patients With Cystic Fibrosis	N/A

Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.