NCT03427086

Brief 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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jan 2018

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 29, 2018

Completed
Same day until next milestone

Study Start

First participant enrolled

January 29, 2018

Completed
11 days until next milestone

First Posted

Study publicly available on registry

February 9, 2018

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 10, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 10, 2021

Completed
Last Updated

September 1, 2021

Status Verified

August 1, 2021

Enrollment Period

3.3 years

First QC Date

January 29, 2018

Last Update Submit

August 27, 2021

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic lateral sclerosisBiotin

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (3)

  • Motor disability measurement

    6 months

  • Change in Pulmonary function test parameters ( FEV1- FVC)

    6 months

  • Weight changes

    6 months

Study Arms (2)

Interventional

ACTIVE COMPARATOR

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

Drug: Biotin

Placebo

PLACEBO COMPARATOR

Patients will receive placebo

Drug: Placebo Oral Tablet

Interventions

BiotinDRUG

High dose biotin

Also known as: vitamin B7
Interventional
Placebo Oral TabletDRUG

Placebo tablet similar in shape and size to the biotin tablet

Also known as: Placebo
Placebo

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

American univeristy of Beirut medical center

Beirut, 1107 2020, Lebanon

Location

Related Publications (10)

  • 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.

    PMID: 20493207BACKGROUND

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

    PMID: 19192301RESULT

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

    PMID: 23217177RESULT

  • 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.

    PMID: 11750036RESULT

  • 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.

    PMID: 19268425RESULT

  • 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.

    PMID: 17182796RESULT

  • 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.

    PMID: 22714021RESULT

  • 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.

    PMID: 23039386RESULT

  • 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.

    PMID: 25787192RESULT

  • 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.

    PMID: 27589059RESULT

Related Links

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Biotin

Condition Hierarchy (Ancestors)

Spinal Cord DiseasesCentral Nervous System DiseasesNervous System DiseasesMotor Neuron DiseaseNeurodegenerative DiseasesTDP-43 ProteinopathiesNeuromuscular DiseasesProteostasis DeficienciesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

ImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsCoenzymesEnzymes and Coenzymes

Study Officials

  • Achraf Makki, MD

    American University of Beirut Medical Center

    PRINCIPAL INVESTIGATOR

  • Johnny Salameh, MD

    American University of Beirut Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
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.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Prospective, double blind, placebo control, randomized 2:1 study
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD

Study Record Dates

First Submitted

January 29, 2018

First Posted

February 9, 2018

Study Start

January 29, 2018

Primary Completion

May 10, 2021

Study Completion

May 10, 2021

Last Updated

September 1, 2021

Record last verified: 2021-08

Locations

LE(1)