Safety and Tolerability of High Dose Biotin in Patients With Amyotrophic Lateral Sclerosis

Summary

This is a randomized double blinded randomized 2:1 study. The duration of the study is 6 month. The safety and tolerability of high doses of biotin (300 mg/ day) will be compared to placebo in patients with amyotrophic lateral sclerosis. Patients will be evaluated at baseline, 3, and 6 month. The primary outcome will be any adverse effects recorded. The secondary outcomes will be motor disability measured by ALS-FRS, change in Pulmonary function test parameters (FEV1- FVC), change in subject weight (in kg).

Timeline

Start

2018-01-29

Primary completion

2021-05-10

Completion

2021-05-10

Publications

• Background Kawamata H, Manfredi G. Mitochondrial dysfunction and intracellular calcium dysregulation in ALS. Mech Ageing Dev. 2010 Jul-Aug;131(7-8):517-26. doi: 10.1016/j.mad.2010.05.003. Epub 2010 May 20.
• Results Wijesekera LC, Leigh PN. Amyotrophic lateral sclerosis. Orphanet J Rare Dis. 2009 Feb 3;4:3. doi: 10.1186/1750-1172-4-3.
• Results Musaro A. Understanding ALS: new therapeutic approaches. FEBS J. 2013 Sep;280(17):4315-22. doi: 10.1111/febs.12087. Epub 2013 Jan 3.
• Results Zimmermann KC, Bonzon C, Green DR. The machinery of programmed cell death. Pharmacol Ther. 2001 Oct;92(1):57-70. doi: 10.1016/s0163-7258(01)00159-0.
• Results Celsi F, Pizzo P, Brini M, Leo S, Fotino C, Pinton P, Rizzuto R. Mitochondria, calcium and cell death: a deadly triad in neurodegeneration. Biochim Biophys Acta. 2009 May;1787(5):335-44. doi: 10.1016/j.bbabio.2009.02.021. Epub 2009 Mar 4.
• Results Atamna H, Newberry J, Erlitzki R, Schultz CS, Ames BN. Biotin deficiency inhibits heme synthesis and impairs mitochondria in human lung fibroblasts. J Nutr. 2007 Jan;137(1):25-30. doi: 10.1093/jn/137.1.25.
• Results Stys PK, Zamponi GW, van Minnen J, Geurts JJ. Will the real multiple sclerosis please stand up? Nat Rev Neurosci. 2012 Jun 20;13(7):507-14. doi: 10.1038/nrn3275.
• Results Luessi F, Siffrin V, Zipp F. Neurodegeneration in multiple sclerosis: novel treatment strategies. Expert Rev Neurother. 2012 Sep;12(9):1061-76; quiz 1077. doi: 10.1586/ern.12.59.
• Results Sedel F, Papeix C, Bellanger A, Touitou V, Lebrun-Frenay C, Galanaud D, Gout O, Lyon-Caen O, Tourbah A. High doses of biotin in chronic progressive multiple sclerosis: a pilot study. Mult Scler Relat Disord. 2015 Mar;4(2):159-69. doi: 10.1016/j.msard.2015.01.005. Epub 2015 Jan 24.
• Results Tourbah A, Lebrun-Frenay C, Edan G, Clanet M, Papeix C, Vukusic S, De Seze J, Debouverie M, Gout O, Clavelou P, Defer G, Laplaud DA, Moreau T, Labauge P, Brochet B, Sedel F, Pelletier J; MS-SPI study group. MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study. Mult Scler. 2016 Nov;22(13):1719-1731. doi: 10.1177/1352458516667568. Epub 2016 Sep 1.

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