AP-HP, Hôpital Henri Mondor, Service de Neurologie, 94010, Créteil, France.
AP-HP, Hôpital Henri Mondor, CRC SEP Grand Paris Est, 94010, Créteil, France.
BMC Neurol. 2023 Oct 30;23(1):389. doi: 10.1186/s12883-023-03440-y.
We proposed to investigate high-dose pharmaceutical-grade biotin in a population of demyelinating neuropathies of different aetiologies, as a proof-of-concept.
Phase IIb open label, uncontrolled, single center, pilot study in 15 patients (three groups of five patients) with chronic demyelinating peripheral neuropathy, i.e. chronic inflammatory demyelinating polyradiculoneuropathy, anti-myelin-associated glycoprotein neuropathy and Charcot-Marie-Tooth 1a or 1b. The investigational product was high-dose pharmaceutical-grade biotin (100 mg taken orally three times a day over a maximum of 52 weeks. The primary endpoint was a 10% relative improvement in 2 of the following 4 electrophysiological variables: motor nerve conduction velocity, distal motor latency, F wave latency, duration of the compound muscle action potential. The secondary endpoints included Overall Neuropathy Limitations Scale (ONLS) score, Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sum score, 10-m walk test, 6-min walk test, posturography parameters, and nerve excitability variables.
The primary endpoint was reached in one patient. In the full population analysis, some secondary endpoints parameters improved: MRC score, INCAT sensory sum score, 6-min walk distance, strength-duration time constant, and rheobase. There was a positive correlation between the improvement in the 6-min walk distance and the strength-duration time constant. Regarding the safety results, 42 adverse events occurred, of which three were of severe intensity but none was considered as related to the investigational product.
Even if the primary endpoint was not met, administration of high-dose pharmaceutical-grade biotin led to an improvement in various sensory and motor parameters, gait abilities, and nerve excitability parameters. The tolerance of the treatment was satisfactory.
ClinicalTrials.gov Identifier: NCT02967679; date 2016/12/05.
我们拟在不同病因脱髓鞘性神经病患者中进行高剂量药物级生物素的研究，以验证其概念。
这是一项在 15 名患者（3 组，每组 5 名）中进行的 IIb 期开放标签、非对照、单中心、试点研究。这些患者患有慢性脱髓鞘性周围神经病，包括慢性炎症性脱髓鞘性多发性神经病、抗髓鞘相关糖蛋白神经病和 Charcot-Marie-Tooth 1a 或 1b 型。研究产品为高剂量药物级生物素（100mg，口服，每日 3 次，最多 52 周）。主要终点是以下 4 个电生理变量中有 2 个相对改善 10%：运动神经传导速度、远端运动潜伏期、F 波潜伏期、复合肌肉动作电位持续时间。次要终点包括总体神经病变限制量表（ONLS）评分、医学研究委员会（MRC）总评分、炎症性神经病病因和治疗（INCAT）感觉总评分、10 米步行试验、6 分钟步行试验、姿势描记术参数和神经兴奋性变量。
主要终点在 1 名患者中达到。在全人群分析中，一些次要终点参数得到改善：MRC 评分、INCAT 感觉总评分、6 分钟步行距离、强度-时间常数和阈值。6 分钟步行距离的改善与强度-时间常数呈正相关。关于安全性结果，共发生 42 例不良事件，其中 3 例为重度，但均未认为与研究药物有关。
即使主要终点未达到，高剂量药物级生物素的给药导致各种感觉和运动参数、步态能力和神经兴奋性参数的改善。治疗的耐受性令人满意。
ClinicalTrials.gov 标识符：NCT02967679；日期 2016 年 12 月 5 日。
