Official Title: “A Phase III Double-Blind, Randomized, Placebo-Controlled Trial of Minocycline in Clinically Isolated Syndromes (CIS)”

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.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment

Study Primary Completion Date: June 2013

- Minocycline 100 mg bid orally compared to identical placebo - Clinically Isolated Syndrome (CIS): Patients with a first clinical demyelinating event suggestive of multiple sclerosis - Men and women, aged 18-50y, first event within the previous 90 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. - 24 months of study drug - Subjects will be permitted to add approved MS disease modifying therapy of their choice (at their own expense) after they reach McDMS. - 14 Canadian MS Clinics - A total of 200 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.

Intervention(s) in this Clinical Trial

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

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1. Minocycline
  • Drug, antibiotic Minocycline Hydrochloride
• Placebo Comparator: 2 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)

Primary 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.
  • Time Frame: 2 years
    Safety Issue?: Yes

Secondary Measures

• To confirm that this early treatment benefit is maintained at two years.
  • Time Frame: 4.7 years
    Safety Issue?: Yes

Inclusion Criteria:

• Age between 18 and 50 years.
• First focal clinical episode suggestive of demyelinating disease within the previous 90 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). The time between the first clinical event and initiation of treatment is reasonably short to prevent loss of patients that convert to MS early.
• While previous CIS studies required earlier enrolment but these studies found that few (about 5 %) patients have a second relapse within 30-60 days of enrolment so we do not expect this extension of the enrolment period to introduce significant bias. On the other hand a 90 day enrolment period increases the generalizability of the results and will improve recruitment.
• At least two lesions on the T2-weighted brain MRI scan with a size of at least 3 mm, at least one of which is ovoid or periventricular or infratentorial. MRI eligibility will be determined centrally by the UBC MS/MRI Research Group.
• 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 50 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Calgary

Overall Clinical Trial Officials and Contacts

Luanne Metz, MD Principal Investigator University of Calgary  

Overall Contact: Luanne Metz, Doctor 403-944-4241 lmetz@ucalgary.ca

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00666887

Study ID Number: Grant ID # 21569

ClinicalTrials.gov Identifier: NCT00666887

Health Authority: Canada: Health Canada