Pain Improvement With Novel Combination Analgesic Regimens (PAIN-CARE): Randomized Controlled Trial Protocol
Bibliographic record
Abstract
BACKGROUND: Neuropathic pain (NP) (including painful diabetic neuropathy, postherpetic neuralgia, etc) affects approximately 7% to 8% of the population and is associated with a devastating symptom burden as well as a profound economic impact for patients, their families, and the health care system. Current therapies have limited efficacy and dose-limiting adverse effects (AEs). Rational combination therapy with carefully selected NP drugs has shown potential for measurable improvements in pain relief, quality of life, and health care use. Today, over half of NP patients concurrently receive 2 or more analgesics but combination use is based on little evidence. Research is urgently needed to identify safer, more effective combinations. OBJECTIVE: We hypothesize that analgesic combinations containing at least 1 nonsedating agent would be as safe but more effective than either monotherapy without increasing overall AEs because of additive pain relief. Pregabalin (PGB), a sedating anticonvulsant, is proven effective for NP; the antioxidant alpha-lipoic acid (ALA) is one of the only nonsedating systemic agents proven effective for NP. Thus, we will conduct a clinical trial to compare a PGB+ALA combination to each monotherapy for NP. METHODS: Using a double-blind, double-dummy, crossover design, 54 adults with NP will be randomly allocated to 1 of 6 sequences of treatment with PGB, ALA and PGB+ALA combination. During each of 3 different treatment periods, participants will take 2 sets of capsules containing (1) ALA or placebo and (2) PGB or placebo for 31 days, followed by an 11-day taper/washout period. The primary outcome will be mean daily pain intensity (0-10) at maximally tolerated dose (MTD) during each period. Secondary outcomes, assessed at MTD, will include global improvement, adverse events, mood, and quality of life. RESULTS: Participant recruitment is expected to begin September 1, 2017. The proposed trial was awarded external peer-reviewed funding by the Canadian Institutes of Health Research (Canada) on July 15, 2016. CONCLUSIONS: This trial will provide rigorous evidence comparing the efficacy of a PGB+ALA combination to PGB alone and ALA alone in the treatment of NP. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number ISRCTN14577546; http://www.isrctn.com/ISRCTN14577546?q=&filters=conditionCategory:Signs%20and%20Symptoms,trialStatus: Ongoing,recruitmentCountry:Canada&sort=&offset=1&totalResults=2&page=1&pageSize=10&searchType=basic-search (Archived by WebCite at http://www.webcitation.org/6qvHFDc6m).
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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 | 0.010 | 0.010 |
| Meta-epidemiology (narrow) | 0.006 | 0.002 |
| Meta-epidemiology (broad) | 0.010 | 0.004 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.002 | 0.003 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.006 | 0.006 |
| Insufficient payload (model declined to judge) | 0.063 | 0.008 |
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".