Minocycline in Clinically Isolated Syndromes (CIS)

Study Overview
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Brief Summary
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The aim of the trial is to demonstrate that 100 mg of oral minocycline twice daily reduces the conversion of CIS to McDonald Criteria MS (McDMS) by an absolute 25% as compared to placebo, over a 6 month follow-up period (primary outcome). A key secondary outcome is to confirm that this early treatment benefit is maintained at two years.

Detailed Description
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Minocycline 100 mg bid orally compared to identical placebo Clinically Isolated Syndrome (CIS): Patients with a first clinical demyelinating event suggestive of multiple sclerosis (At baseline participants may meet 2010 McDonald diagnostic criteria for MS, but not 2005 criteria) Men and women, aged 18-60y, first event within the previous 180 days; brain magnetic resonance imaging (MRI) with at least two brain T2 lesions which are at least 3 mm in diameter, and at least one of which is ovoid or periventricular or infratentorial. Up to 24 months of study drug (Up to 12 months of study drug for patients recruited after December 31, 2012) Patients will be discontinued from the study when they convert to McDMS based on the 2005 McDonald definition. 12 Canadian MS Clinics A total of 154 patients will be randomized. Because 30% of screened patients with CIS who are clinically eligible are not expected to meet the MRI criteria for inclusion, up to 280 patients will be screened.

Official Title
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A Phase III Double-blind, Randomized, Placebo-controlled Trial of Minocycline in Clinically Isolated Syndromes (CIS) and Early Single Relapse Multiple Sclerosis (MS)

Conditions
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Clinically Isolated Syndromes, Early Single Relapse of Multiple Sclerosis

Intervention / Treatment
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* Drug: Minocycline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 60 years. First focal clinical episode suggestive of demyelinating disease within the previous 180 days (measured from onset of the first symptom to treatment start), based on the appearance of a neurological abnormality, present for at least 24 hours. Objective clinical evidence must be present or documented. Patients will be included irrespective of whether the first clinical demyelinating episode was monosymptomatic (i.e. clinical evidence of a single lesion) or polysymptomatic (i.e. clinical evidence of more than one lesion). At least two lesions on the T2-weighted brain MRI* scan at least one of which is ovoid or periventricular or infratentorial. MRI eligibility will be determined centrally by the UBC MS/MRI Research Group.*One lesion on spinal MRI may substitute for one brain lesion as per the 2005 McDonald Criteria. Sexually active women of child-bearing potential must agree to use adequate contraception. Written informed consent Exclusion Criteria: Any disease other than MS that could better explain the patient's signs and symptoms. Any previous clinical event reasonably attributable to acute demyelination, regardless of whether medical attention was obtained. Complete transverse myelitis or bilateral optic neuritis. A waiver can be obtained for bilateral optic neuritis but must be obtained prior to randomization. Waivers must be approved by 3 neurologists including a member of the Clinical Eligibility / Endpoint Committee, a member of the DSMC, and by an experienced MS neurophthalmologist.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Minocycline<br>Minocycline 100 mg oral for up to 24 months | Drug: Minocycline<br>* 100 mg twice daily to be taken for up to 2 years<br>* Other names: Minocycline Hydrochloride;|
| Placebo Comparator: Placebo<br>Lactose Monohydrate NF (Spray-dried) 235 mg/cap Magnesium Stearate NF 1 mg/cap Croscarmellose Sodium NF 4 mg/cap Stearic Acid 10 mg/cap Placebo CAP Lt orange OP-Purple OP (APO 100) | Drug: Placebo<br>* placebo twice daily for 2 years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To demonstrate that 100 mg of oral minocycline twice daily reduces the conversion of CIS to McDonald Criteria MS (McDMS) by an absolute 25% as compared to placebo, over a 6 month follow-up period. |  | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To confirm that this early treatment benefit is maintained at two years. |  | 2 years | 
| Change in T2 lesion volume |  | 6 months and 24 months | 
| Cumulative number of enhancing T1 lesions |  | 6 months and 24 months | 
| cumulative combined unique lesions (new enhancing T1-weighted lesions plus new and enlarging T2 lesions, without lesion double counting) |  | 6 months and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, Clinically Isolated Syndrome, Minocycline, Placebo