Randomized Trial of Minocycline for Clinically Isolated Syndrome and Early Single Relapse Multiple Sclerosis: Study Design, Participant Characteristics, and Recruitment Challenges (P1.227)
Bibliographic record
Abstract
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
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.004 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.009 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".