[P1.227] Randomized Trial of Minocycline for Clinically Isolated Syndrome and Early Single Relapse Multiple Sclerosis: Study Design, Participant Characteristics, and Recruitment Challenges
Luanne M. Metz,1Anthony Traboulsee,2David Li,2Pierre Duquette,3Michael Yeung,1Marcelo Kremenchutzky,4Galina Vorobeychik,5Mark Freedman,6Virender Bhan,7Gregg Blevins,8James Marriott,9Francois Grand'Maison,10Liesly Lee,11Manon Thibault,12Misha Eliasziw,13V. Wee Yong,1Graziela Cerchiaro,1Samuel Wiebe,1Yan Cheng,2Guojun Zhao,2Jamie Greenfield,1Marites Topor,1Andrew Riddehough2
1Calgary, AB, Canada, 2Vancouver, BC, Canada, 3Montreal, QC, Canada, 4London, ON, Canada, 5Burnaby, BC, Canada, 6Ottawa, ON, Canada, 7Halifax, NS, Canada, 8Edmonton, AB, Canada, 9Winnipeg, MB, Canada, 10Greenfield Park, QC, Canada, 11Toronto, ON, Canada, 12Sillery, QC, Canada, 13Boston, MA, USA
OBJECTIVE: This phase III double-blind, randomized clinical trial (NCT00666887) aims to demonstrate that minocycline reduces the conversion of clinically isolated syndrome (CIS) to multiple sclerosis (MS) by 25% compared to placebo within 6 months. Follow-up continues to 2 years. We describe the trial design, participant characteristics and recruitment challenges.
BACKGROUND: Minocycline is a widely available oral drug that appears promising for relapsing remitting MS.
DESIGN/METHODS: Patients from 12 Canadian MS clinics, aged 18 to 60 years who had a first focal episode of demyelination within the previous 180 days, and at least two lesions on T2-weighted brain screening magnetic resonance imaging (MRI), were randomized (1:1) to minocycline 100 mg twice daily or matching placebo. After the screening and baseline visits, follow-up occurred at 1, 3, 6, 12, 18, and 24 months. MRI scans were obtained at screening, 3, 6, 12, and 24 months.
RESULTS: This trial began in 2008 and will be completed in December 2014. Over 55 months, 236 patients were screened and 143 randomized. This was 92% of the recruitment target. The majority of screen failures were due to fewer than 2 lesions on cranial MRI (57%) or reaching the 2005 McDonald criteria for MS (the study endpoint) before randomization (24%). Mean age of the randomized group was 36 years (range: 18-56), 69% were women, mean CIS duration was 65 days (range: 4-183), median EDSS was 1.5 (range: 0-4.5), and 59% were randomized to the high risk strata (2 or more enhancing lesions or dissemination in space based on 2005 McDonald criteria). These characteristics did not change over time. Ten patients remain in follow-up to month 6. Only 12 patients (8.4%) discontinued participation before reaching month 6 indicating excellent retention.
CONCLUSIONS: Recruitment was challenging as the diagnostic criteria for MS changed and new therapies became available. Despite the length of the trial, participant characteristics remained comparable over the enrolment period.
Study Supported by: Multiple Sclerosis Society of Canada
Category - MS and CNS Inflammatory Disease: Clinical Science
Monday, April 28, 2014 3:00 PM
P1: Poster Session I: MS and CNS inflammatory Disease: Clinically Isolated Syndromes (3:00 PM-6:30 PM)