Minocycline in Clinically Isolated Syndromes (CIS)

Clinically Isolated Syndromes Clinical Trial

— MinoCIS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00666887
• Other study ID #: Grant ID # 21569
• Secondary ID: Health Canada Co
• Status: Completed
• Phase: Phase 3
• First received: April 23, 2008
• Last updated: February 23, 2017
• Start date: January 2009
• Est. completion date: July 2015

Study information

• Verified date: February 2017
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

• 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 142
• Est. completion date: July 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Clinically Isolated Syndromes
• Early Single Relapse of Multiple Sclerosis
• Multiple Sclerosis
• Recurrence
• Sclerosis
• Syndrome

Intervention

Drug:
• Minocycline
100 mg twice daily to be taken for up to 2 years
• Placebo
placebo twice daily for 2 years

Locations

Country	Name	City	State
Canada	Fraser Health Multiple Sclerosis Clinic	Burnaby	British Columbia
Canada	University of Calgary, Calgary Health Region	Calgary	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	Clinique Neuro Rive-Sud	Greenfield Park	Quebec
Canada	Dalhousie MS Research Unit	Halifax	Nova Scotia
Canada	MS Clinic, London Health Sciences Centre	London	Ontario
Canada	CHUM Notre-Dame	Montreal	Quebec
Canada	The Ottawa Hospital, Multiple Sclerosis Research Clinic	Ottawa	Ontario
Canada	CHAUQ Enfant-Jesus	Quebec City	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	UBC Hospital	Vancouver	British Columbia
Canada	MS Research Unit, Health Sciences Centre	Winnipeg	Manitoba

Sponsors (2)

Lead Sponsor	Collaborator
Dr. Luanne Metz	Multiple Sclerosis Society of Canada

Country where clinical trial is conducted

Canada, 

Outcome

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