Minocycline in Clinically Isolated Syndromes (CIS)

NCT00666887 | Completed Phase 3 DMC

• 2 other identifiers: Grant ID # 21569Health Canada Control #120007
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 12

Brief Summary

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.

Conditions

Clinically Isolated Syndromes; Early Single Relapse of Multiple Sclerosis

Keywords

Multiple Sclerosis; Clinically Isolated Syndrome; Minocycline; Placebo

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

Study Arms (2)

Minocycline

ACTIVE COMPARATOR

Minocycline 100 mg oral for up to 24 months

Drug: Minocycline

Placebo

PLACEBO COMPARATOR

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

Interventions

Minocycline DRUG

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

Also known as: MINOCIN, Minocycline Hydrochloride

Minocycline

Placebo DRUG

placebo twice daily for 2 years

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dr. Luanne Metz: lead
• Multiple Sclerosis Society of Canada: collaborator

Study Sites (12)

University of Calgary, Calgary Health Region

Calgary, Alberta, T2N 4N1, Canada

Location

University of Alberta

Edmonton, Alberta, T6G 2G3, Canada

Location

Fraser Health Multiple Sclerosis Clinic

Burnaby, British Columbia, V5G 2X6, Canada

Location

UBC Hospital

Vancouver, British Columbia, V6T 2B5, Canada

Location

MS Research Unit, Health Sciences Centre

Winnipeg, Manitoba, R3A 1R9, Canada

Location

Dalhousie MS Research Unit

Halifax, Nova Scotia, B3H 1V7, Canada

Location

MS Clinic, London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

Location

The Ottawa Hospital, Multiple Sclerosis Research Clinic

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Clinique Neuro Rive-Sud

Greenfield Park, Quebec, J4V2J2, Canada

Location

CHUM Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

CHAUQ Enfant-Jesus

Québec, Quebec, G1J 1Z4, Canada

Location

Related Publications (3)

• 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.

  PMID: 35848622 DERIVED

• 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.

  PMID: 28564557 DERIVED

• 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.

  PMID: 23970502 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis; cyclopia sequence

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Luanne Metz, MD

  University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 23, 2008
• First Posted: April 25, 2008
• Study Start: January 1, 2009
• Primary Completion: December 1, 2014
• Study Completion: July 1, 2015
• Last Updated: February 27, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (12)