PRECISE trial (Pain RElief Combination Intervention StratEgies): protocol for the clinical trial of a pregabalin–melatonin combination for fibromyalgia
Bibliographic record
Abstract
INTRODUCTION: Fibromyalgia is associated with chronic widespread pain and disturbed sleep. Multidisciplinary, multimodal management often includes pharmacotherapy; however, current drugs used to treat fibromyalgia provide meaningful benefit to only 30-60% of treated individuals. Combining two or more different drugs is common in clinical practice with the expectation of better efficacy, tolerability or both; however, further research is needed to identify which combinations actually provide added benefit. Thus, we are planning a clinical trial to evaluate melatonin (MLT)-pregabalin (PGB) combination in participants with fibromyalgia. METHODS AND ANALYSIS: This will be a single-centre, double-blind, randomised, double-dummy, three-period, crossover trial comparing a MLT-PGB combination to each monotherapy in 54 adult participants satisfying the 2016 American College of Rheumatology criteria for fibromyalgia. Participants will receive maximally tolerated doses of MLT, PGB and MLT-PGB combination for 6 weeks. The primary outcome will be daily pain intensity (0-10); secondary outcomes will include the Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events and other measures. Analysis of the primary and secondary outcomes will involve a linear mixed model with sequence, period, treatment, the first-order carryover and baseline pain score as fixed effects and participant as a random effect to test whether there are any treatment differences among three treatments and to estimate the least square mean of the mean daily pain intensity for each treatment, adjusting for carryover as well as period effects (ie, stability of pain levels). ETHICS AND DISSEMINATION: This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN #18278231, has been granted ethical approval by the Queen's University Health Sciences Research Ethics Board (Queen's HSREB Protocol #6040998) and is currently under review for a Clinical Trial Application to Health Canada Natural and Non-prescription Health Products Directorate. All participants will provide written informed consent prior to trial participation. Following trial completion, results will be disseminated in one or more biomedical journal publications and presented at one or more scientific meetings. TRIAL REGISTRATION NUMBER: This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN18278231.
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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 | 0.024 | 0.022 |
| Meta-epidemiology (narrow) | 0.006 | 0.003 |
| Meta-epidemiology (broad) | 0.009 | 0.005 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.003 | 0.003 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.004 | 0.002 |
| Research integrity | 0.007 | 0.008 |
| Insufficient payload (model declined to judge) | 0.149 | 0.031 |
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".