IMI2-PainCare-BioPain-RCT3: a randomized, double-blind, placebo-controlled, crossover, multi-center trial in healthy subjects to investigate the effects of lacosamide, pregabalin, and tapentadol on biomarkers of pain processing observed by electroencephalography (EEG).
Background: IMI2-PainCare-BioPain-RCT3 is one of four similarly designed clinical studies aiming at profiling a set of functional biomarkers of drug effects on the nociceptive system that could serve to accelerate the future development of analgesics, by providing a quantitative understanding betwee...
| Publicado en: | Trials Vol. 22; no. 1; pp. 1 - 32 |
|---|---|
| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research randomized controlled trial Journal Article |
| Publicado: |
BioMed Central
6/17/2021
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=150972857&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 150972857 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 17456215 38OC jtl: Trials issn: 17456215 maglogo: N pubinfo: dt: 6/17/2021 vid: 22 iid: 1 pid: 24147 pub: BioMed Central artinfo: ui: 150972857 150972857 NLM34140041 150972857 10.1186/s13063-021-05272-y NLM34140041 150972857 ppf: 1 ppct: 31 formats: tig: atl: IMI2-PainCare-BioPain-RCT3: a randomized, double-blind, placebo-controlled, crossover, multi-center trial in healthy subjects to investigate the effects of lacosamide, pregabalin, and tapentadol on biomarkers of pain processing observed by electroencephalography (EEG). aug: au: Mouraux, André Bloms-Funke, Petra Boesl, Irmgard Caspani, Ombretta Chapman, Sonya C. Di Stefano, Giulia Finnerup, Nanna Brix Garcia-Larrea, Luis Goetz, Marcus Kostenko, Anna Pelz, Bernhard Pogatzki-Zahn, Esther Schubart, Karin Stouffs, Alexandre Truini, Andrea Tracey, Irene Troconiz, Iñaki F. Van Niel, Johannes Vela, Jose Miguel Vincent, Katy affil: Institute of Neuroscience (IoNS), UCLouvain, Brussels, Belgium sug: subj: Electroencephalography Pain Research Subjects Human Pain Measurement Crossover Design Double-Blind Studies Comparative Studies Multicenter Studies Randomized Controlled Trials Evaluation Research Validation Studies Clinical Assessment Tools Scales ab: Background: IMI2-PainCare-BioPain-RCT3 is one of four similarly designed clinical studies aiming at profiling a set of functional biomarkers of drug effects on the nociceptive system that could serve to accelerate the future development of analgesics, by providing a quantitative understanding between drug exposure and effects of the drug on nociceptive signal processing in human volunteers. IMI2-PainCare-BioPain-RCT3 will focus on biomarkers derived from non-invasive electroencephalographic (EEG) measures of brain activity.Methods: This is a multisite single-dose, double-blind, randomized, placebo-controlled, 4-period, 4-way crossover, pharmacodynamic (PD) and pharmacokinetic (PK) study in healthy subjects. Biomarkers derived from scalp EEG measurements (laser-evoked brain potentials [LEPs], pinprick-evoked brain potentials [PEPs], resting EEG) will be obtained before and three times after administration of three medications known to act on the nociceptive system (lacosamide, pregabalin, tapentadol) and placebo, given as a single oral dose in separate study periods. Medication effects will be assessed concurrently in a non-sensitized normal condition and a clinically relevant hyperalgesic condition (high-frequency electrical stimulation of the skin). Patient-reported outcomes will also be collected. A sequentially rejective multiple testing approach will be used with overall alpha error of the primary analysis split between LEP and PEP under tapentadol. Remaining treatment arm effects on LEP or PEP or effects on EEG are key secondary confirmatory analyses. Complex statistical analyses and PK-PD modeling are exploratory.Discussion: LEPs and PEPs are brain responses related to the selective activation of thermonociceptors and mechanonociceptors. Their amplitudes are dependent on the responsiveness of these nociceptors and the state of the pathways relaying nociceptive input at the level of the spinal cord and brain. The magnitude of resting EEG oscillations is sensitive to changes in brain network function, and some modulations of oscillation magnitude can relate to perceived pain intensity, variations in vigilance, and attentional states. These oscillations can also be affected by analgesic drugs acting on the central nervous system. For these reasons, IMI2-PainCare-BioPain-RCT3 hypothesizes that EEG-derived measures can serve as biomarkers of target engagement of analgesic drugs for future Phase 1 clinical trials. Phase 2 and 3 clinical trials could also benefit from these tools for patient stratification.Trial Registration: This trial was registered 25/06/2019 in EudraCT ( 2019%2D%2D001204-37 ). pubtype: Academic Journal doctype: research randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|