P154 TRPV1 is not a Target for the Treatment of non-allergic Rhinitis: A Clinical Study
Bibliographic record
Abstract
<h3>Background</h3> TRPV1 is a ligand gated ion channel activated by a range of physiological factors such at Temperature, pH, and osmotic stress. In the nose, the TRPV1-expressing sensory c-fibres are thought to play a key role in the development of nasal hyper-responsiveness resulting in symptoms in NAR patients. We hypothesise that topical antagonism with a selective TRPV1 antagonist would offer substantial symptom control. SB705498 is a potent selective TRPV1 antagonist in animal and human models. <h3>Methods</h3> 40 M&F NAR patients were enrolled into a randomised, double-blind, placebo controlled, 2 period crossover study of either 12mg SB705498 i.n. or placebo for 14 days with a 4 week washout. The study was conducted in a validated Environmental Challenge Chamber (Cetero) where patients were exposed to Cold Dry Air (CDA) at 14c, 15% RH, air speed 5 feet/sec. Exposure was over the winter months in Canada. Diary card symptoms were analysed during home dosing on days when the temp was less than 14c. Two chamber sessions of 1hr duration, as well as medical history and neg skin prick testing, at screening were performed to establish a consistent diagnosis with a single challenge on Day 1+1hr, Day14+1hr and Day 14+24hr to establish the drug response. Post dose TSS (rhinorrhoea, congestion, PND), sneezing and ocular symptoms were recorded, as was acoustic rhinomanometry, RQLQ, PK and Safety monitoring. <h3>Results</h3> The primary outcome of weighted mean TSS over the challenge period or the maximum TSS was not impacted by administration of SB705498 relative to placebo (see figure). There was no impact on sneezing, ocular symptoms, acoustic rhinimanometry, or RQLQ Compared with placebo, repeated doses of SB705498 did not alleviate TSS triggered by cold in a multistimuli wild type setting. PK analysis supported an o.d. regimen with 2 fold accumulation over the dosing period. <h3>Conclusions</h3> In a robust clinical model of non-allergic rhinitis, intranasal SB705498 12mg o.d. for 14 days did not alleviate the symptoms of NAR triggered by the most common provocation agent: Cold Dry Air. We conclude that despite engagement of the TRPV1 receptor there was no translation to clinical efficacy, suggesting redundancy in symptom pathways.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".