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Minocycline in Clinically Isolated Syndromes (CIS) (MinoCIS)

Primary Purpose

Clinically Isolated Syndromes, Early Single Relapse of Multiple Sclerosis

Status
Completed
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Minocycline
Placebo
Sponsored by
Dr. Luanne Metz
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Clinically Isolated Syndromes focused on measuring Multiple Sclerosis, Clinically Isolated Syndrome, Minocycline, Placebo

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Calgary, Calgary Health Region
  • University of Alberta
  • Fraser Health Multiple Sclerosis Clinic
  • UBC Hospital
  • MS Research Unit, Health Sciences Centre
  • Dalhousie MS Research Unit
  • MS Clinic, London Health Sciences Centre
  • The Ottawa Hospital, Multiple Sclerosis Research Clinic
  • Sunnybrook Health Sciences Centre
  • Clinique Neuro Rive-Sud
  • CHUM Notre-Dame
  • CHAUQ Enfant-Jesus

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Minocycline

Placebo

Arm Description

Minocycline 100 mg oral for up to 24 months

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

To confirm that this early treatment benefit is maintained at two years.
Change in T2 lesion volume
Cumulative number of enhancing T1 lesions
cumulative combined unique lesions (new enhancing T1-weighted lesions plus new and enlarging T2 lesions, without lesion double counting)

Full Information

First Posted
April 23, 2008
Last Updated
February 23, 2017
Sponsor
Dr. Luanne Metz
Collaborators
Multiple Sclerosis Society of Canada
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1. Study Identification

Unique Protocol Identification Number
NCT00666887
Brief Title
Minocycline in Clinically Isolated Syndromes (CIS)
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
July 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Dr. Luanne Metz
Collaborators
Multiple Sclerosis Society of Canada

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clinically Isolated Syndromes, Early Single Relapse of Multiple Sclerosis
Keywords
Multiple Sclerosis, Clinically Isolated Syndrome, Minocycline, Placebo

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
142 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Minocycline
Arm Type
Active Comparator
Arm Description
Minocycline 100 mg oral for up to 24 months
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Minocycline
Other Intervention Name(s)
MINOCIN, Minocycline Hydrochloride
Intervention Description
100 mg twice daily to be taken for up to 2 years
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo twice daily for 2 years
Primary Outcome Measure Information:
Title
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.
Time Frame
6 Months
Secondary Outcome Measure Information:
Title
To confirm that this early treatment benefit is maintained at two years.
Time Frame
2 years
Title
Change in T2 lesion volume
Time Frame
6 months and 24 months
Title
Cumulative number of enhancing T1 lesions
Time Frame
6 months and 24 months
Title
cumulative combined unique lesions (new enhancing T1-weighted lesions plus new and enlarging T2 lesions, without lesion double counting)
Time Frame
6 months and 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Luanne Metz, MD
Organizational Affiliation
University of Calgary
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Calgary, Calgary Health Region
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N1
Country
Canada
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2G3
Country
Canada
Facility Name
Fraser Health Multiple Sclerosis Clinic
City
Burnaby
State/Province
British Columbia
ZIP/Postal Code
V5G 2X6
Country
Canada
Facility Name
UBC Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6T 2B5
Country
Canada
Facility Name
MS Research Unit, Health Sciences Centre
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3A 1R9
Country
Canada
Facility Name
Dalhousie MS Research Unit
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 1V7
Country
Canada
Facility Name
MS Clinic, London Health Sciences Centre
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5A5
Country
Canada
Facility Name
The Ottawa Hospital, Multiple Sclerosis Research Clinic
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Clinique Neuro Rive-Sud
City
Greenfield Park
State/Province
Quebec
ZIP/Postal Code
J4V2J2
Country
Canada
Facility Name
CHUM Notre-Dame
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 4M1
Country
Canada
Facility Name
CHAUQ Enfant-Jesus
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1J 1Z4
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Consent to share IPD was not obtained from subjects so data cannot be shared except amongst investigators.
Citations:
PubMed Identifier
35848622
Citation
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.
Results Reference
derived
PubMed Identifier
28564557
Citation
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.
Results Reference
derived
PubMed Identifier
23970502
Citation
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.
Results Reference
derived

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Minocycline in Clinically Isolated Syndromes (CIS)

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