Effects of Selective Sphingosine‐1‐Phosphate Receptor 1 Agonist, TRV045 , on Evoked Pain Tests: An Exploratory, Four‐Way Cross‐Over Study in Healthy Volunteers
Abstract
Introduction: Preclinical evidence suggests that dysregulation of the ceramide-sphingosine-1-phosphate (S1P) axis may have analgesic properties. However, currently approved S1PR1 modulators such as fingolimod are hindered for this indication as they induce lymphopenia. The aim of the current study was to evaluate whether the novel, selective S1PR1 agonist TRV045 has analgesic effects in a validated evoked pain test battery in healthy volunteers.
Methods: In this randomized, double-blind, double-dummy, placebo-controlled, four-way cross-over study, 25 male or female healthy volunteers were randomized to receive either placebo or TRV045 50, 150 or 300 mg at separate occasions. The primary endpoint was heat pain detection threshold on UVB-induced inflammatory pain. Secondary endpoints included analgesic reduction of capsaicin-induced allodynia and pain detection and tolerance thresholds to evoked cold, electrical, pressure and heat pain. Furthermore, safety, tolerability and pharmacokinetics were monitored throughout the study. Data analyses included a repeated-measures mixed-effects model.
Results: TRV045 was well tolerated, without serious adverse events. Compared to placebo, TRV045 did not reduce heat pain detection thresholds on UVB-exposed skin, but significantly reduced the secondary area of capsaicin-induced pain for the higher dose levels: 150 mg: -304.10 mm2 (95% CI: -494.78 to -113.43, p = 0.002); 300 mg: -298.51 mm2 (-486.83 to -110.20, p = 0.002). No effects on…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
Read the paper
Related studies
- Noninvasive and Point-of-Care Surface-Enhanced Raman Scattering (SERS)-Based Breathalyzer for Mass Screening of Coronavirus Disease 2019 (COVID-19) under 5 min
- De Novo Transcriptome Analysis and Detection of Antimicrobial Peptides of the American Cockroach Periplaneta americana (Linnaeus)
- Molecular Characterization and Expression Profiling of Tomato GRF Transcription Factor Family Genes in Response to Abiotic Stresses and Phytohormones
- Assembly of Tight Junction Strands: Claudin-10b and Claudin-3 Form Homo Tetrameric Building Blocks that Polymerise in a Channel-Independent Manner
- Update of the Pompe variant database for the prediction of clinical phenotypes: Novel disease‐associated variants, common sequence variants, and results from newborn screening
- Machine Learning-Based SERS Chemical Space for Two-Way Prediction of Structures and Spectra of Untrained Molecules
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.