2024-514896-17-00招募中2 期
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
Centre D'Etude Des Cellules Souches2 个研究点 分布在 2 个国家目标入组 23 人开始时间: 2024年11月19日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 23
- 试验地点
- 2
- 主要终点
- Preservation of auditory function defined as no decrease higher than 5 dB in hearing at 8 kHz in high frequency average (HFA) over three years, assessed by audiometry tests (PTA) and High frequency pure tone audiometry hearing test (HFPTA) in patients with Wolfram syndrome with a deficit of at least 20d dB at 8 kHz treated with VPA at optimal dose corresponding to the plasma level between 40 and 100 mg/l (i.e., 300 to 700 micro mol/l).
研究概览
简要总结
Preservation of auditory function defined as no decrease higher than 5 dB in hearing at 8 kHz in high frequency average (HFA) over three yearsin patients with Wolfram syndrome with deficit of at least 20 dB at 8 kHz treated with an optimal dose of VPA corresponding to the plasma level between 40 and 100 mg/l (ie, 300 to 700 micromol/l).
入排标准
- 年龄范围
- 0 years 至 64 years（0-17 Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •The patient has a definite diagnosis of Wolfram syndrome, as determined by the following: a. Documented diabetes mellitus diagnosed under 16 completed years according to WHO or ADA criteria OR documented optic atrophy diagnosed under 16 completed years AND b. 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(WOCBP)(ie fertile, following menarche, until becoming post-menoposal unless permanently sterile, according to the CTFG guidelines on contraception) who are prescribed sodium valproate must use effective contraception without interruption during the entire duration of treatment and at least until 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 before inclusion. 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 must be used in case of heterosexual intercourse.
- •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 pregnancy tests at each study visit. Additional urinary pregnancy tests may be performed according to local pregnancy prevention program with Depakine.
- •Sexually active male patients with a female partner of childbearing potential must agree to the use of condoms and the use of an 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.
排除标准
- •The patient is unable or unwilling to comply with the protocol requirements
- •An unwillingness on the part of male patients to use highly effective form of birth control if engaging in sexual intercourse with a woman who could become pregnant from the time of the first dose of study medication until completion of follow-up procedures.
- •An unwillingness on the part of female patients to use highly effective form of birth control if engaging in sexual intercourse and to have frequent pregnancy tests during treatment and until completion of follow-up procedures.
- •The patient is currently pregnant or breastfeeding
- •Patient with severe swallowing disorders
- •The patient has received treatment with any investigational drug within the 30 days prior to the screening visit
- •The patient is currently taking VPA
- •The patient has an history of allergy or hypersensitivity to VPA or its excipients/ingredients
- •The patient is known to be affected by a pathology for which the symptoms or associated treatments can alter the hearing function and/or affect the ear
- •The patient has clinically significant non-Wolfram related CNS involvement which is judged by the Investigator to be likely to interfere with the accurate administration and interpretation of protocol assessments
- •The patient has a contra-indication to VPA: mitochondrial disorders caused by mutations in the nuclear gene encoding the mitochondrial enzyme polymerase γ (POLG), e.g. Alpers-Huttenlocher Syndrome, active liver disease, personal or family history of liver dysfunction related to known genetic disorders, porphyria, lactose intolerance, the Lapp lactase deficiency, glucose- galactose malabsorption, urea cycle disorders…
- •Any other acute or chronic medical, psychiatric, social situation or laboratory result that, based on Investigator's judgment, would jeopardize patient safety during trial participation, cause inability to comply with the protocol, or affect the Trial participation
- •The patient has a known history of severe central apnea with apnea/hypopnea index (AHI)>30
结局指标
主要结局
Preservation of auditory function defined as no decrease higher than 5 dB in hearing at 8 kHz in high frequency average (HFA) over three years, assessed by audiometry tests (PTA) and High frequency pure tone audiometry hearing test (HFPTA) in patients with Wolfram syndrome with a deficit of at least 20d dB at 8 kHz treated with VPA at optimal dose corresponding to the plasma level between 40 and 100 mg/l (i.e., 300 to 700 micro mol/l).
Preservation of auditory function defined as no decrease higher than 5 dB in hearing at 8 kHz in high frequency average (HFA) over three years, assessed by audiometry tests (PTA) and High frequency pure tone audiometry hearing test (HFPTA) in patients with Wolfram syndrome with a deficit of at least 20d dB at 8 kHz treated with VPA at optimal dose corresponding to the plasma level between 40 and 100 mg/l (i.e., 300 to 700 micro mol/l).
次要结局
- Safety: Overall incidence of adverse events and serious adverse events, patient withdrawals as well as changes from baseline in laboratory safety assessments and vital signs parameters will be evaluated for each group and for the study as a whole.
- Efficacy: Ventral Pons Volume measured and recorded in mm3 by standardised analysis of MRI at baseline, at visit 6 (Week 52) and at the last visit
- Efficacy: Insulin and or desmopressin requirements will be assessed whenever the patient is under one or both treatments in order to document potential benefit from VPA on diabetes mellitus or diabetes insipidus
- Efficacy: Visual acuity will be assessed using standard ETDRS measures and visual field recording at baseline, every six months during the first year of follow-up and at the final visit
- Efficacy: Retinal nerve thickness measure by OCT measures at baseline, every six months during the first year of follow-up and at the final visit
- Efficacy: Balance, measured by Mini-BESTest (Appendix 1) at baseline, at visit 6 (Week 52) and at the final visit
- Efficacy: Sleep will be investigated by a specific Sleep questionnaire at baseline, at visit 6 (Week 52) and final visit, for patients under 18 years: sleeping habits measured by the Pediatric Sleep Questionnaire (PSQ) Parent Questionnaire, and for adults: sleeping habits, measured by the Pittsburg Sleep Quality Index (PSQI) Self-Report
研究者
General Manager
Scientific
Centre D'Etude Des Cellules Souches
研究点 (2)
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