Evaluation of the Incidence of Relapses in Patients With Biotin-treated Progressive Multiple Sclerosis (IPBio-SeP)

Background: High dose biotin is a therapeutic option for French progressive Multiple Sclerosis (MS) patients, without relapse for at least one year, since June 1, 2016. Despite the inflammatory activity of progressive forms of MS is known to be low, several publications mentioned clinical and/or radiological activity for biotin-treated patients.

Objectives:

1. To determine if high dose biotin increase the clinical inflammatory activity of patients with a progressive form of MS.
2. To compare the clinical characteristics of the relapses that occurred with biotin or not.
3. To describe the characteristics of the patients with a clinical inflammatory activity with biotin.

Methods: This is a national, academic, observational and retrospective study comparing one group of progressive MS patients with high dose biotin to another group without this treatment using a propensity score, in intention to treat. The main judgment criterion is the annualized relapse rate (ARR) from the beginning of the biotin to the last evaluation available before the data extraction. A Student's t test will be used. A negative binomial modelling with relapses counting over a period of exposure and taking into account the inter and intra center variability will be used. The statistical tests will be adapted to the nature of the variables concerning the secondary judgment criteria.

Expected results: This French national study will provide a better knowledge of the inflammatory activity of the progressive forms of MS treated with high dose biotin. If an increased clinical inflammatory activity is highlighted with biotin a prospective study will be necessary to confirm the result before a specific information of the scientific community and the patients about this risk or even an amendment of prescription rules in order to secure the use of the product. On the contrary, the absence of increased risk of clinical inflammatory activity with biotin would help to reassure the prescriber and the patient about the innocuity of the treatment.

Study Overview

• Status: Unknown
• Conditions: Progressive Multiple Sclerosis
• Intervention / Treatment: Drug: biotin; Other: propensity score

Detailed Description

Investigators are going to recruit retrospectively all the patients treated with biotin since the product is available in France, in all French MS centers that agree to participate (maximum 30). They are going to collect through medical records, demographic data (as age, gender, MS center localization), but also data about the disease (as MS duration, primary progressive or secondary progressive MS), data about disability (with several Expanded Disability Status Scale -EDSS- scores at different time points) and data about treatments (as duration of biotin, existence of other concomitant disease-modifying therapy). For comparison, a control group without biotin is going also to be recruited from the European Database for Multiple Sclerosis (EDMUS). The same data as described above are going to be collected for the controls.

• Study Type: Observational
• Enrollment (Anticipated): 3000

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63003
    • Chu Clermont-Ferrand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with Progressive forms of Multiple Sclerosis

Description

Inclusion Criteria:

• For the patients treated with biotin :
• progressive form of MS (primary or secondary)
• age between 18 and 80 years
• Expanded Disability Status Scale (EDSS) between 3 and 7.5 at the beginning of biotin
• treatment with biotin 300 mg per day at least one time, ongoing or stopped
• no relapse in the year preceding biotin introduction
• follow-up in an MS expert center
• For the controls :
• progressive form of MS (primary or secondary)
• age between 18 and 80 years
• Expanded Disability Status Scale (EDSS) between 3 and 7.5 at the baseline
• EDMUS data base fulfilled at least three times during the two previous years
• no relapse in the year preceding the baseline
• follow-up in an MS expert center

Exclusion Criteria:

• For all participants :
• other disease modifying therapy (DMT) than interferon, methotrexate, mycophenolate mofetil, azathioprine, rituximab, ocrelizumab
• For the controls :
• treatment with biotin actually or in the past
• follow-up in an MS expert center who do not provide exhaustive information about biotin

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients treated with biotin; This is a national, academic, observational and retrospective study comparing one group of progressive MS patients with high dose biotin to another group without this treatment using a propensity score, in intention to treat	Drug: biotin; This is a national, academic, observational and retrospective study comparing one group of progressive MS patients with high dose biotin to another group without this treatment using a propensity score, in intention to treat.
Control patients; This is a national, academic, observational and retrospective study comparing one group of progressive MS patients with high dose biotin to another group without this treatment using a propensity score, in intention to treat	Other: propensity score; This is a national, academic, observational and retrospective study comparing one group of progressive MS patients with high dose biotin to another group without this treatment using a propensity score, in intention to treat.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapses with biotin	To determine if high dose biotin increases the clinical inflammatory activity of patients with a progressive form of MS using the annualized relapse rate (ARR) comparing to a control group	at day 1 (through study completion, an average of 1 year)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical characteristics of the relapses with biotin	To compare the clinical characteristics of the relapses that occurred with biotin or not.	at day 1 (through study completion, an average of 1 year)
Characteristics of patients with relapse with biotin	To describe the characteristics of the patients with a clinical inflammatory activity with biotin	at day 1 (through study completion, an average of 1 year)

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: MedDay Pharmaceuticals SA; OFSEP (Observatoire Français de la Sclérose en Plaques); SFSEP (Société Francophone de la Sclérose en Plaques)

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 30, 2018
• Primary Completion (ANTICIPATED): February 1, 2019
• Study Completion (ANTICIPATED): April 30, 2019

Study Registration Dates

• First Submitted: April 25, 2018
• First Submitted That Met QC Criteria: May 29, 2018
• First Posted (ACTUAL): June 11, 2018

Study Record Updates

• Last Update Posted (ACTUAL): June 11, 2018
• Last Update Submitted That Met QC Criteria: May 29, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Relapse; Biotin; Progressive Multiple Sclerosis
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease Attributes; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Recurrence; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Biotin
• Other Study ID Numbers: CHU-388

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No