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

Primary Purpose

Amyotrophic Lateral Sclerosis

Status

Completed

Phase

Phase 2

Locations

Lebanon

Study Type

Interventional

Intervention

Biotin

Placebo Oral Tablet

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring Amyotrophic lateral sclerosis, Biotin

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

American univeristy of Beirut medical center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Interventional

Placebo

Arm Description

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

Patients will receive placebo

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

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.

Weight changes

Changes in body weight (in kilograms) will be measured in both study arms

Full Information

NCT ID

NCT03427086

First Posted

January 29, 2018

Last Updated

August 27, 2021

Sponsor

American University of Beirut Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT03427086

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2021

Overall Recruitment Status

Completed

Study Start Date

January 29, 2018 (Actual)

Primary Completion Date

May 10, 2021 (Actual)

Study Completion Date

May 10, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

American University of Beirut Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic lateral sclerosis, Biotin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Prospective, double blind, placebo control, randomized 2:1 study

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

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.

Allocation

Randomized

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Interventional

Arm Type

Active Comparator

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Patients will receive placebo

Intervention Type

Drug

Intervention Name(s)

Biotin

Other Intervention Name(s)

vitamin B7

Intervention Description

High dose biotin

Intervention Type

Drug

Intervention Name(s)

Placebo Oral Tablet

Other Intervention Name(s)

Placebo

Intervention Description

Placebo tablet similar in shape and size to the biotin tablet

Primary Outcome Measure Information:

Title

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Description

Any adverse effects resulting from receiving high dose biotin in patients with amyotrophic lateral sclerosis will be recorded

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Motor disability measurement

Description

Time Frame

6 months

Title

Change in Pulmonary function test parameters ( FEV1- FVC)

Description

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.

Time Frame

6 months

Title

Weight changes

Description

Changes in body weight (in kilograms) will be measured in both study arms

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Achraf Makki, MD

Organizational Affiliation

American University of Beirut Medical Center

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Johnny Salameh, MD

Organizational Affiliation

American University of Beirut Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

American univeristy of Beirut medical center

City

Beirut

ZIP/Postal Code

1107 2020

Country

Lebanon

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

20493207

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.

Results Reference

background

PubMed Identifier

19192301

Citation

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

Results Reference

result

PubMed Identifier

23217177

Citation

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 Reference

result

PubMed Identifier

11750036

Citation

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 Reference

result

PubMed Identifier

19268425

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.

Results Reference

result

PubMed Identifier

17182796

Citation

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 Reference

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PubMed Identifier

22714021

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. Erratum In: Nat Rev Neurosci. 2012 Aug;13(8):597.

Results Reference

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PubMed Identifier

23039386

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.

Results Reference

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PubMed Identifier

25787192

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.2015.01.005. Epub 2015 Jan 24.

Results Reference

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PubMed Identifier

27589059

Citation

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.

Results Reference

result

Links:

URL

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

Description

Circulation and Energy Metabolism of the Brain

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

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