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.
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 patient has a definite diagnosis of Wolfram syndrome, as determined by the following:
⁃ Documented diabetes mellitus diagnosed under 16 completed years according to WHO or ADA criteria OR documented optic atrophy diagnosed under 16 completed years AND Documented functionally relevant mutations on one or both alleles of the WFS1 gene based on historical test results (if available) or from a qualified laboratory at screening
• The patient has sensorineural hearing loss of at least 20 db at 8 kHz in HFA
• The patient is 13 years of age or older, and has a body-weight over 37.5 kg
• Written informed consent for the principal study
• Women of childbearing potential who are prescribed with sodium valproate must use effective contraception without interruption during the entire duration of treatment and at least 90 days after last administration . These patients will be provided with comprehensive information on pregnancy prevention and will be referred for contraceptive advice if they are not using effective contraception. At least one effective method of contraception (preferably a user independent form such as an intra-uterine device or implant) or two complementary forms of contraception including a barrier method should be used.
• Women with childbearing potential are required to have a confirmed negative blood pregnancy test before starting medication administration at baseline. Women with childbearing potential agree to repeat blood pregnancy tests during at each study visit.
• Sexually active men with a female partner of childbearing potential must agree to the use of condoms and the use of a effective method of contraception by the female partner.
• Patient willing and able to meet all protocol defined visits for the duration of the Trial.
• Patients with active hearing implants, containing a magnetic system are allowed to participate to study, and will not have MRI during study participation.