Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Oct 30;23(1):389.
doi: 10.1186/s12883-023-03440-y.

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

Alain Créange  1   2   3 , Emilie Hutin  4   5 , Frédéric Sedel  6 , Ludivine Le Vigouroux  7 , Jean-Pascal Lefaucheur  8   9   10
Affiliations

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

Alain Créange et al. BMC Neurol. .

Abstract

Background: We proposed to investigate high-dose pharmaceutical-grade biotin in a population of demyelinating neuropathies of different aetiologies, as a proof-of-concept.

Methods: 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.

Results: 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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov Identifier: NCT02967679; date 2016/12/05.

Keywords: Biotin; CMT neuropathy; Demyelination; Inflammatory neuropathy; Nerve excitability; Peripheral neuropathies.

PubMed Disclaimer

Conflict of interest statement

AC reports grants and nonfinancial support from Medday, during the conduct of the study; personal fees from Medday, personal fees from Merck, grants from Octapharma, grants and personal fees from Novartis, grants and personal fees from Roche, and grants and personal fees from Biogen, outside the submitted work.

EH has nothing to disclose.

FS was employee and shareholder of Medday; personal fees from medday pharmaceuticals, outside the submitted work; In addition, FS has a patent Pharmaceutical Compositions highly dosed with Biotin EP2555771/ US 20130084334 with royalties paid to Medday, a patent Method of treating Amyotrophic Lateral Sclerosis and neuropathies with Biotin EP 3273957/ US 20190314342 issued, and a patent Methods of Treating Multiple Sclerosis with Biotin EP2729143/US 20140030331 with royalties paid to Medday.

LLV is an employee of ATLANSTAT.

JPL has nothing to disclose.

Figures

Fig. 1
Fig. 1
Participant flowchart
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Stys PK, Waxman SG, Ransom BR. Na(+)-Ca2+ exchanger mediates Ca2+ influx during anoxia in mammalian central nervous system white matter. Ann Neurol. 1991;30(3):375–380. doi: 10.1002/ana.410300309. - DOI - PubMed
    1. Smith KJ, Kapoor R, Hall SM, Davies M. Electrically active axons degenerate when exposed to nitric oxide. Ann Neurol. 2001;49(4):470–476. doi: 10.1002/ana.96. - DOI - PubMed
    1. Lefaucheur JP, Boërio D, Hogrel JY, Créange A. Nerve excitability studies in the assessment of dysimmune neuropathies. Rev Neurol (Paris). 2006;162(Suppl. 1). Spec No 1:3S17–3S26. - PubMed
    1. Boerio D, Creange A, Hogrel JY, Gueguen A, Bertrand D, Lefaucheur JP. Nerve excitability changes after intravenous immunoglobulin infusions in multifocal motor neuropathy and chronic inflammatory demyelinating neuropathy. J Neurol Sci. 2010;292(1–2):63–71. doi: 10.1016/j.jns.2010.02.002. - DOI - PubMed
    1. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society--First Revision. J Peripher Nerv Syst 2010;15(1):1–9. - PubMed

MeSH terms

Associated data