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

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03427086
• Other study ID #: BIO-2017-0270
• Status: Completed
• Phase: Phase 2
• Start date: January 29, 2018
• Est. completion date: May 10, 2021

Study information

• Verified date: August 2021
• Source: American University of Beirut Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: May 10, 2021
• Est. primary completion date: May 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Amyotrophic Lateral Sclerosis (ALS) volunteers must be diagnosed within 3 years prior to participation as having possible, probable, or definite ALS, either sporadic or familial according to modified El Escorial criteria

• Age 18-80, able to provide informed consent, and comply with study procedures

• Participants must not have started Riluzole and/or Nuedexta for at least 30 days, or be on a stable dose of Riluzole and/or Nuedexta for at least 30 days, prior to screening (Riluzole and/or Nuedexta -naïve participants are permitted in the study)

Exclusion Criteria:

• The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair ability of the participant to provide informed consent, according to PI judgment.

• Exposure to any experimental agent within 30 days of entry or at any time during the trial or enrollment in another research study within 30 days of or during this trial.

• Slow Vital Capacity test less than 50% of the predicted value Patients who had already undergone tracheostomy

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• Biotin
High dose biotin
• Placebo Oral Tablet
Placebo tablet similar in shape and size to the biotin tablet

Locations

Country	Name	City	State
Lebanon	American univeristy of Beirut medical center	Beirut

Sponsors (1)

Lead Sponsor	Collaborator
American University of Beirut Medical Center

Country where clinical trial is conducted

Lebanon, 

References & Publications (10)

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. Review. — View Citation

Musarò A. Understanding ALS: new therapeutic approaches. FEBS J. 2013 Sep;280(17):4315-22. doi: 10.1111/febs.12087. Epub 2013 Jan 3. Review. — View Citation

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 — View Citation

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. Review. Erratum in: Nat Rev Neurosci. 2012 Aug;13(8):597. — View Citation

Tourbah A, Lebrun-Frenay C, Edan G, Clanet M, Papeix C, Vukusic S, De Sèze 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 p — View Citation

Wijesekera LC, Leigh PN. Amyotrophic lateral sclerosis. Orphanet J Rare Dis. 2009 Feb 3;4:3. doi: 10.1186/1750-1172-4-3. Review. — View Citation

Zimmermann KC, Bonzon C, Green DR. The machinery of programmed cell death. Pharmacol Ther. 2001 Oct;92(1):57-70. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Any adverse effects resulting from receiving high dose biotin in patients with amyotrophic lateral sclerosis will be recorded	6 months
Secondary	Motor disability measurement	The motor disability will be measured in the both arms using the revised amyotrophic lateral sclerosis functional rating scale (ALS-FRSr). This scale measures the progression and the severity of the disease. It is compose of 12 questions, each questions can have a score from 0 to 4. Questions 1 to 3 are related to bulbar onset, questions 4 to 9 are related to limb onset and questions 10-12 are related to respiratory onset. The minimum score is 0 and the maximum total score is 48. The higher the score the better the functional status. The lower the score the worse the functional status of the patient.	6 months
Secondary	Change in Pulmonary function test parameters ( FEV1- FVC)	Forced expiratory volume in 1 second (FEV1) measured in percents and forced vital capacity (FVC) measured in liters will be measured in the both study arms.	6 months
Secondary	Weight changes	Changes in body weight (in kilograms) will be measured in both study arms	6 months

External Links

•   Circulation and Energy Metabolism of the Brain