NCT04940572

Efficacy Study of Daily Administration of VPA in Patients Affected by Wolfram Syndrome

AUDIOWOLF: A Phase II, Open-label, Efficacy Study of Daily Administration of Sodium Valproate in Patients Clinically Affected by Wolfram Syndrome Due to Monogenic Mutation.

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 23 (estimated)
• Sponsor: Centre d'Etude des Cellules Souches · Academic / Other
• Sex: All
• Age: 13 Years
• Healthy volunteers: Not accepted

Summary

Open label, phase II study non randomized single group assignment of 20 evaluable patients 13 years and older, over 37,5 kg body-weight, with sensorineural hearing loss of at least 20 dB at 8 kHz in high frequency average (HFA), and with documented genetic mutations in the WFS1 gene and with at least one other major documented clinical symptom pertaining to Wolfram syndrome (i.e. diabetes mellitus, diabetes insipidus, optic atrophy). Every patients will receive over three years a treatment by VPA (Depakine chrono).

Detailed description

Open label, phase II study non randomized single group assignment of 20 evaluable patients 13 years and older, over 37,5 kg body-weight, with sensorineural hearing loss of at least 20 dB at 8 kHz in high frequency average (HFA), AND with documented genetic mutations in the WFS1 gene AND with at least one other major documented clinical symptom pertaining to Wolfram syndrome (i.e. diabetes mellitus, diabetes insipidus, optic atrophy). Every patients will receive over three years a treatment by VPA (Depakine chrono). The effective dose and duration of this 3 years therapy has to be determined individually with the aim to obtain preservation of auditory function defined as no decrease higher than 5 dB on one ear compared to baseline at 8 kHz on high frequencies average and to reduce the dose of insulin and/or desmopressin needed, therefore monitoring of the patients plasma concentration of VPAis required for dose adjustment. Generally a plasma level between 40 and 100 mg/l (ie, 300 to 700 micromol/l) sodium valproate is aimed to be reached. Initially 10-15 mg of sodium valproate/kg bodyweight per day will be taken in one or two doses during meals. The dose will then be increased every 3 days in steps of 10 mg sodium valproate/kg bodyweight per day till the optimal plasma level is reached but does not exceed 100 milligrams per liter (ie, 700 micromol/l) during 156 weeks (refer to Appendix 5). Analysis will compare Pure tone audiometry (PTA), Speech interference index (SII) and High frequency pure tone audiometry hearing test between baseline and final visit.

Conditions

• Wolfram Syndrome

Interventions

Type	Name	Description
DRUG	Depakine	Refer to arm description.

Timeline

• Start date: 2021-11-26
• Primary completion: 2025-11-01
• Completion: 2025-12-01
• First posted: 2021-06-25
• Last updated: 2023-11-28

Locations

2 sites across 2 countries: France, Spain