Update on the progress of IMI-PainCare, a public-private partnership supported by the European Union to improve the care of patients with acute or chronic pain. EFIC is one of about 40 partners of this consortium (www.imi-paincare.eu):
Within IMI-PainCare, subproject BioPain aims to improve the translation between preclinical and clinical stages of analgesic drug development through the use of biomarkers of nervous system function. These are used within the project to identify changes caused by multiple classes of analgesics, specifically within pain relevant pathways. Pharmacokinetic-pharmacodynamic (PK-PD) modelling of this data is being used to assess the effects of these analgesics in comparable rodent and humans studies, and will identify the potential of these underutilized techniques to facilitate future trials of novel analgesics.
The four multicenter clinical trials are nearing completion. Each trial is run in three or four of the six countries where the BioPain academic partners are located (Germany, Denmark, Belgium, Italy, France and Great Britain). All four trials are collecting data on modulation of nociceptive signal processing by lacosamide, pregabalin and tapentadol vs. placebo. Outcomes of these double-blind studies are expected later this year. The trial designs are published (Mouraux et al. 2021, Nochi et al. 2022). Test-retest reliability has been assessed so far for peripheral nerve excitability in motor, large sensory and small sensory fibers, and for laser-evoked potentials and pinprick-evoked potentials. Spinal biomarkers (RIII reflex, N13 somatosensory evoked potential), were found to be sensitive to modulation by central sensitization (inhibited by pregabalin) and endogenous pain controls (Di Lionardo et al. 2021, Leone et al. 2021, Pietro et al. 2021). Along with preclinical data, some of these findings were presented at the EFIC Congress in Dublin, which led to a lively discussion with the audience on how the functional biomarkers can be integrated in clinical practice and future trials in patients. It was agreed that on one hand, some of the biomarkers may be sensitive to diagnose spinal excitability in patients, while on the other hand biomarkers that are sensitive to change by drug treatment may be useful surrogate endpoints independent of their diagnostic value. Stratification of patients according to observable signs of underlying mechanisms is getting closer to being a reality.
The equivalent preclinical studies are also progressing well, with data collection complete for the peripheral nerve excitability experiments (threshold tracking). Partial datasets have also been obtained for the other three biomarkers (spinal evoked potentials, laser evoked potentials and oxygen amperometry). Completion of these remaining studies is expected within a similar timeframe to the clinical trials.
EFIC is a consortium member of all three IMI PainCare subprojects and actively supports the project by giving scientific advice, fostering PR, and dissemination.
References:
- Pietro GD et al. (2021) Neurophysiologie Clin 51(6): 517-523
- Leone C et al. (2021) Clin Neurophys 132(12): 2989-2995
- DiLionardo A et al. (2021) Scientific Reports 11(1): 20838
- Mouraux A et al. (2021) Trials. 2021 Jun 17;22(1):404. PMID: 34140041
- Nochi Z et al. (2022) Trials. 2022 Feb 19;23(1):163. PMID: 35183242
