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

NCT ID: NCT03427086

Last Updated: 2021-09-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-01-29

Study Completion Date

2021-05-10

Brief Summary

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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).

Detailed Description

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Conditions

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Amyotrophic Lateral Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective, double blind, placebo control, randomized 2:1 study
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
The subjects, care givers, investigator, and coordinator will be blinded. The pharmacist, who will be responsible for the drug supply, will be unblinded. The investigational drug and the placebo will have identical pill shape and color. They will be supplied in identical boxes.

Study Groups

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Interventional

Patient will received high dose of biotin (300 mg/day)

Group Type ACTIVE_COMPARATOR

Biotin

Intervention Type DRUG

High dose biotin

Placebo

Patients will receive placebo

Group Type PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type DRUG

Placebo tablet similar in shape and size to the biotin tablet

Interventions

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Biotin

High dose biotin

Intervention Type DRUG

Placebo Oral Tablet

Placebo tablet similar in shape and size to the biotin tablet

Intervention Type DRUG

Other Intervention Names

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vitamin B7 Placebo

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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American University of Beirut Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Johnny Salameh

MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Achraf Makki, MD

Role: PRINCIPAL_INVESTIGATOR

American University of Beirut Medical Center

Johnny Salameh, MD

Role: PRINCIPAL_INVESTIGATOR

American University of Beirut Medical Center

Locations

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American univeristy of Beirut medical center

Beirut, , Lebanon

Site Status

Countries

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Lebanon

References

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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.

Reference Type BACKGROUND
PMID: 20493207 (View on PubMed)

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

Reference Type RESULT
PMID: 19192301 (View on PubMed)

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

Reference Type RESULT
PMID: 23217177 (View on PubMed)

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.

Reference Type RESULT
PMID: 11750036 (View on PubMed)

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.

Reference Type RESULT
PMID: 19268425 (View on PubMed)

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.

Reference Type RESULT
PMID: 17182796 (View on PubMed)

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.

Reference Type RESULT
PMID: 22714021 (View on PubMed)

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.

Reference Type RESULT
PMID: 23039386 (View on PubMed)

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.

Reference Type RESULT
PMID: 25787192 (View on PubMed)

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.

Reference Type RESULT
PMID: 27589059 (View on PubMed)

Related Links

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https://www.ncbi.nlm.nih.gov/books/NBK20413/

Circulation and Energy Metabolism of the Brain

Other Identifiers

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BIO-2017-0270

Identifier Type: -

Identifier Source: org_study_id

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