Minocycline in Clinically Isolated Syndromes (CIS)

NCT ID: NCT00666887

Last Updated: 2017-02-27

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

PHASE3

Total Enrollment

142 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-01-31

Study Completion Date

2015-07-31

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.

Conditions

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Clinically Isolated Syndromes Early Single Relapse of Multiple Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Minocycline

Minocycline 100 mg oral for up to 24 months

Group Type ACTIVE_COMPARATOR

Minocycline

Intervention Type DRUG

100 mg twice daily to be taken for up to 2 years

Placebo

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)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

placebo twice daily for 2 years

Interventions

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Minocycline

100 mg twice daily to be taken for up to 2 years

Intervention Type DRUG

Placebo

placebo twice daily for 2 years

Intervention Type DRUG

Other Intervention Names

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MINOCIN Minocycline Hydrochloride

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Multiple Sclerosis Society of Canada

OTHER

Sponsor Role collaborator

Dr. Luanne Metz

OTHER

Sponsor Role lead

Responsible Party

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Dr. Luanne Metz

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Luanne Metz, MD

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Locations

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University of Calgary, Calgary Health Region

Calgary, Alberta, Canada

Site Status

University of Alberta

Edmonton, Alberta, Canada

Site Status

Fraser Health Multiple Sclerosis Clinic

Burnaby, British Columbia, Canada

Site Status

UBC Hospital

Vancouver, British Columbia, Canada

Site Status

MS Research Unit, Health Sciences Centre

Winnipeg, Manitoba, Canada

Site Status

Dalhousie MS Research Unit

Halifax, Nova Scotia, Canada

Site Status

MS Clinic, London Health Sciences Centre

London, Ontario, Canada

Site Status

The Ottawa Hospital, Multiple Sclerosis Research Clinic

Ottawa, Ontario, Canada

Site Status

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status

Clinique Neuro Rive-Sud

Greenfield Park, Quebec, Canada

Site Status

CHUM Notre-Dame

Montreal, Quebec, Canada

Site Status

CHAUQ Enfant-Jesus

Québec, Quebec, Canada

Site Status

Countries

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Canada

References

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Camara-Lemarroy C, Metz L, Kuhle J, Leppert D, Willemse E, Li DK, Traboulsee A, Greenfield J, Cerchiaro G, Silva C, Yong VW. Minocycline treatment in clinically isolated syndrome and serum NfL, GFAP, and metalloproteinase levels. Mult Scler. 2022 Nov;28(13):2081-2089. doi: 10.1177/13524585221109761. Epub 2022 Jul 18.

Reference Type DERIVED
PMID: 35848622 (View on PubMed)

Metz LM, Li DKB, Traboulsee AL, Duquette P, Eliasziw M, Cerchiaro G, Greenfield J, Riddehough A, Yeung M, Kremenchutzky M, Vorobeychik G, Freedman MS, Bhan V, Blevins G, Marriott JJ, Grand'Maison F, Lee L, Thibault M, Hill MD, Yong VW; Minocycline in MS Study Team. Trial of Minocycline in a Clinically Isolated Syndrome of Multiple Sclerosis. N Engl J Med. 2017 Jun 1;376(22):2122-2133. doi: 10.1056/NEJMoa1608889.

Reference Type DERIVED
PMID: 28564557 (View on PubMed)

Kang H, Metz LM, Traboulsee AL, Eliasziw M, Zhao GJ, Cheng Y, Zhao Y, Li DK; Minocycline in CIS Study Group. Application and a proposed modification of the 2010 McDonald criteria for the diagnosis of multiple sclerosis in a Canadian cohort of patients with clinically isolated syndromes. Mult Scler. 2014 Apr;20(4):458-63. doi: 10.1177/1352458513501230. Epub 2013 Aug 22.

Reference Type DERIVED
PMID: 23970502 (View on PubMed)

Other Identifiers

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Health Canada Control #120007

Identifier Type: OTHER

Identifier Source: secondary_id

Grant ID # 21569

Identifier Type: -

Identifier Source: org_study_id

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