The aim of this study is to assess the anti-hyperalgesic effect of dextromethorphan in healthy volunteers compared to placebo.
This is a cross-over group, double-blind, randomized clinical trial in healthy volunteers comparing dextromethorphan and inactive control on freeze-induced hyperalgesia, experimental pain, diffuse noxious inhibitory control (DNIC), pupillary reaction and reaction time. The influence of CYP3A4 and MDR1 polymorphism on the dextromethorphan analgesic efficacy will be measured. The study design is divided in two study sequences and each subject participates in the two study sequences and receive the two treatments (dextromethorphan and placebo). Each study sequence consists of 3 assessment days (Day -1, Day 0 = first treatment administration and Day 1).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
20
The study design is divided in two study sequences and each subject participates in the two study sequences and receive the two treatments (dextromethorphan and placebo).
The study design is divided in two study sequences and each subject participates in the two study sequences and receive the two treatments (dextromethorphan and placebo).
CHU Clermont-Ferrand
Clermont-Ferrand, France
Area under the curve (AUC) of percentage changes in mechanical pain thresholds (MPT) using electronic von frey in secondary hyperalgesic zone (Z2)
Time frame: at Day 0 after treatment administration: 1 hour post-dose (T0+1h), 2 hours post-dose (T0+2h) and 3 hours post-dose (T0+3h).
Area under the curve (AUC) of percentage changes in mechanical pain thresholds (MPT) using electronic von frey in control skin zone (Z0) and primary hyperalgesic zone (Z1)
Time frame: at D0 T0+1h, T0+2h and T0+3h after treatment administration
Percentage changes in mechanical pain thresholds (MPT) using electronic von frey in control skin zone (Z0)
Time frame: at Day 0 after treatment administration: 1 hour post-dose (T0+1h), 2 hours post-dose (T0+2h) and 3 hours post-dose (T0+3h).
Percentage changes in mechanical pain thresholds (MPT) using electronic von frey in primary hyperalgesic zone (Z1)
Time frame: at Day 0 30 min before treatment (T0-30min ) and at Day 0 after treatment administration: 1 hour post-dose (T0+1h), 2 hours post-dose (T0+2h) and 3 hours post-dose (T0+3h) and at Day 1 after treatment administration: 24,5 hours post-dose (T0+24h30).
Conditioned Pain Modulation (CPM) assessment
Time frame: at Day -1 before treatment and Day 0 30 min before treatment (T0-30min)
Reaction time assessment using RTI CANTAB® test
Time frame: at Day -1 before treatment and Day 0 30 min before treatment (T0-30min), after treatment administration: 1 hour post-dose (T0+1h) and 3 hours post-dose (T0+3h) and at Day 1 after treatment administration: 24,5 hours post-dose (T0+24h30).
Determination of potential central effects of dextromethorphan measuring pupillary reaction
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Determination of potential central effects of dextromethorphan measuring pupillary reaction assessing the diameter of the pupil in real time in scotopic conditions (e.g. size variation \[mm\]; contraction speed \[mm.s-1\]; contraction latency \[ms\]) at Day 0 30 min before treatment (T0-30min ) and at Day 0 after treatment administration: 1 hour post-dose (T0+1h), 2 hours post-dose (T0+2h) and 3 hours post-dose (T0+3h) and at Day 1 after treatment administration: 24,5 hours post-dose (T0+24h30). \- Study of genetic polymorphism of cytochrome P450 3A4 and MDR1 gene through study completion, up to 6 months.
Time frame: at Day 0 30 min before treatment (T0-30min ) and at Day 0 after treatment administration: 1 hour post-dose (T0+1h), 2 hours post-dose (T0+2h) and 3 hours post-dose (T0+3h) and at Day 1 after treatment administration: 24,5 hours post-dose (T0+24h30).
Study of genetic polymorphism of cytochrome P450 3A4 and genetic polymorphism of MDR1 gene
Time frame: up to 6 months.
Dosage of plasma concentration of dextromethorphan and dextromethorphan's metabolites from blood collections
Time frame: at Day 0 30 min before treatment (T0-30min ) and at Day 0 after treatment administration: 2 hours post-dose (T0+2h) and at Day 1 after treatment administration: 24,5 hours post-dose (T0+24h30).