Clinically Isolated SyndromesPhase 3MinoCISNCT00666887
Minocycline in Clinically Isolated Syndromes (CIS)
A Phase 3 study testing Minocycline in people with Clinically Isolated Syndromes and Early Single Relapse of Multiple Sclerosis, run by Dr. Luanne Metz at 12 sites in Canada.
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). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Clinically Isolated Syndromes, Early Single Relapse of Multiple Sclerosis
- What is being tested?
- Minocycline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 142 participants
- Where
- 12 sitesCanada
- Study dates
- Jan 2009to Jul 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Canada12 sites
Fraser Health Multiple Sclerosis Clinic
Burnaby, British Columbia, V5G 2X6
University of Calgary, Calgary Health Region
Calgary, Alberta, T2N 4N1
University of Alberta
Edmonton, Alberta, T6G 2G3
Clinique Neuro Rive-Sud
Greenfield Park, Quebec, J4V2J2
Dalhousie MS Research Unit
Halifax, Nova Scotia, B3H 1V7
MS Clinic, London Health Sciences Centre
London, Ontario, N6A 5A5
CHUM Notre-Dame
Montreal, Quebec, H2L 4M1
The Ottawa Hospital, Multiple Sclerosis Research Clinic
Ottawa, Ontario, K1H 8L6
CHAUQ Enfant-Jesus
Québec, Quebec, G1J 1Z4
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
UBC Hospital
Vancouver, British Columbia, V6T 2B5
MS Research Unit, Health Sciences Centre
Winnipeg, Manitoba, R3A 1R9
About this study
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)
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.
Read the 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.
- Being tested
- Minocycline, Placebo
- Keywords
- Multiple Sclerosis, Clinically Isolated Syndrome, Minocycline, Placebo
- Medical subject headings
- Multiple Sclerosis, cyclopia sequence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MinocyclineDrug
Also called MINOCIN, Minocycline Hydrochloride
100 mg twice daily to be taken for up to 2 years
PlaceboDrug
placebo twice daily for 2 years
| Study group | Role | What they receive |
|---|---|---|
| Minocycline | Active comparator | Minocycline 100 mg oral for up to 24 months Receives: 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) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 Months
Secondary outcomes (4)
To confirm that this early treatment benefit is maintained at two years.
Measured: 2 years
Change in T2 lesion volume
Measured: 6 months and 24 months
Cumulative number of enhancing T1 lesions
Measured: 6 months and 24 months
cumulative combined unique lesions (new enhancing T1-weighted lesions plus new and enlarging T2 lesions, without lesion double counting)
Measured: 6 months and 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2008 (estimated)
- Study startJan 2009
- Primary completionDec 2014
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Clinically Isolated SyndromesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 142 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Luanne Metz
- Sponsor type
- University, hospital or other
- Collaborators
- Multiple Sclerosis Society of Canada
- Responsible party
- Sponsor-investigator, Dr. Luanne Metz, University of Calgary
- Investigators
- Luanne Metz, MD, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00666887
- Sponsor's protocol ID
- Grant ID # 21569
- Other IDs
- Health Canada Control #120007
- Acronym
- MinoCIS
- Status last verified
- Feb 2017
- First submitted
- 23 Apr 2008
- Last updated
- 27 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: Consent to share IPD was not obtained from subjects so data cannot be shared except amongst investigators.
Publications
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.
PubMed 35848622Metz 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.
PubMed 28564557Kang 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.
PubMed 23970502
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00666887
- Acronym / sponsor ID
- MinoCIS / Grant ID # 21569
- Keywords
- Multiple Sclerosis, Clinically Isolated Syndrome, Minocycline, Placebo
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 142 participants (actual)
- Lead sponsor
- Dr. Luanne MetzUniversity, hospital or other
- Collaborators
- Multiple Sclerosis Society of Canada
- Study start
- Jan 2009
- Primary completion
- Dec 2014 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 25 Apr 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Minocycline | Active comparator | Drug: MinocyclineMinocycline 100 mg oral for up to 24 months |
| Placebo | Placebo comparator | Drug: PlaceboLactose 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) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MinocyclineAlso: MINOCIN, Minocycline Hydrochloride100 mg twice daily to be taken for up to 2 years | Drug | Minocycline |
| Placeboplacebo twice daily for 2 years | Drug | Placebo |
Primary outcome
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
4 secondary outcomes
To confirm that this early treatment benefit is maintained at two years.
Time frame: 2 years
Change in T2 lesion volume
Time frame: 6 months and 24 months
Cumulative number of enhancing T1 lesions
Time frame: 6 months and 24 months
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2017.
- Derived from this study: PubMed 35848622Camara-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.
- Derived from this study: PubMed 28564557Metz 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.
- Derived from this study: PubMed 23970502Kang 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.
- Individual participant dataSharing planned: No. Consent to share IPD was not obtained from subjects so data cannot be shared except amongst investigators.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luanne Metz, MD principal investigator
University of Calgary
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Minocycline in people with Clinically Isolated Syndromes and Early Single Relapse of Multiple Sclerosis, run by Dr. Luanne Metz at 12 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00666887, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2017.