High-dose pharmaceutical-grade biotin in patients with demyelinating neuropathies: a phase 2b open label, uncontrolled, pilot study

BMC Neurology

Research

Jean-Pascal Lefaucheur¹  Alain Créange²  Ludivine Le Vigouroux³  Emilie Hutin⁴  Frédéric Sedel⁵ 

[1] AP-HP, Hôpital Henri Mondor, CRC SEP Grand Paris Est, 94010, Créteil, France;Université Paris Est Créteil, EA4391, ENT, F-94010, Créteil, France;AP-HP, Hôpital Henri Mondor, Unité de Neurophysiologie Clinique, 94010, Créteil, France;AP-HP, Hôpital Henri Mondor, Service de Neurologie, 94010, Créteil, France;AP-HP, Hôpital Henri Mondor, CRC SEP Grand Paris Est, 94010, Créteil, France;Université Paris Est Créteil, EA4391, ENT, F-94010, Créteil, France;ATLANSTAT, Rezé, France;Laboratoire Analyse Et Restauration du Mouvement, Service de Rééducation Neurolocomotrice, AP-HP, Hôpital Henri Mondor, 94010, Créteil, France;Université Paris Est Créteil, EA 7377, BIOTN, F-94010, Créteil, France;Medday Pharmaceuticals, Paris, France;

关键词: Biotin;    Peripheral neuropathies;    Demyelination;    Nerve excitability;    Inflammatory neuropathy;    CMT neuropathy;   

DOI  :  10.1186/s12883-023-03440-y

 received in 2023-07-24, accepted in 2023-10-18,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundWe proposed to investigate high-dose pharmaceutical-grade biotin in a population of demyelinating neuropathies of different aetiologies, as a proof-of-concept.MethodsPhase 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.ResultsThe 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.ConclusionsEven 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.Trial registrationClinicalTrials.gov Identifier: NCT02967679; date 2016/12/05.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 5

12951_2017_297_Article_IEq1.gif