Hydex: Dextromethorphan Effect on Central Sensitization to Pain in Healthy Volunteers

Sponsor

University Hospital, Clermont-Ferrand (Other)

Overall Status

Completed

CT.gov ID

NCT02596360

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of this study is to assess the anti-hyperalgesic effect of dextromethorphan in healthy volunteers compared to placebo.

Condition or Disease	Intervention/Treatment	Phase
Experimental Pain Hyperalgesia	Drug: Pulmodexane® 30mg Drug: lactose	Phase 1

Detailed Description

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 Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Dextromethorphan Effect on Central Sensitization to Pain in Healthy Volunteers

Study Start Date :

Nov 1, 2015

Actual Primary Completion Date :

Mar 1, 2016

Actual Study Completion Date :

Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dextromethorphan 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).	Drug: Pulmodexane® 30mg 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).
Placebo Comparator: 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).	Drug: lactose 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).

Arm

Intervention/Treatment

Experimental: Dextromethorphan

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).

Drug: Pulmodexane® 30mg

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).

Placebo Comparator: 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).

Drug: lactose

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).

Outcome Measures

Primary Outcome Measures

Area under the curve (AUC) of percentage changes in mechanical pain thresholds (MPT) using electronic von frey in secondary hyperalgesic zone (Z2) [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).]

Secondary Outcome Measures

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) [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) [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) [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 [at Day -1 before treatment and Day 0 30 min before treatment (T0-30min)]
Reaction time assessment using RTI CANTAB® test [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 [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).]
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.
Study of genetic polymorphism of cytochrome P450 3A4 and genetic polymorphism of MDR1 gene [up to 6 months.]
Dosage of plasma concentration of dextromethorphan and dextromethorphan's metabolites from blood collections [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).]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy male volunteers
Aged between 18 and 45 years
CYP2D6 Extensive and Intermediate metabolizers
Body mass index (BMI) between 19 and 30 kg/m2
Systolic blood pressure between 100 and 150 mmHg, diastolic blood pressure between 50 and 90 mmHg, heart rate between 45 and 90 beats per minute
Without treatment during the 7 days before inclusion specially no use of analgesic and anti-inflammatory drugs
Cooperation and understanding enough to conform to the study obligations
Having given free informed written consent
Affiliated to the French Social Security
Inscription or acceptation of inscription in the national register of volunteers involved in trials.

Exclusion Criteria:

Hypersensitivity to the active substance or to any of the excipients
Lactose intolerance
Hypertension
History of stroke
Severe heart failure
Severe hepatic impairment
Shortness of breath
Congenital galactosemia, glucose-galactose malabsorption, lactase deficiency
Association with linezolid
Pre-existence or history of peripheral neuropathy due to a cause different from neurotoxic chemotherapy
Diabetes (type I and II)
CYP2D6 Poor and Ultra-rapid metabolizers
AST, ALT, total bilirubin twice the average
Dextromethorphan intake during the 7 days before inclusion
Medical and surgical history incompatible with the study
Disease progression during inclusion
Excessive consumption of alcohol (> 50g/day), tobacco (≥ 10 cigarettes/day), coffee, tea or drinks with caffeine (equivalent to more than 4 cups a day) or any addiction to drugs
Subject lacking concentration during tests training and low test results reproducibility
Subject does not meet the selection criteria for its ability to discriminate sensations to noxious stimuli during psychometric tests
Subject exclusion period, or the total allowable compensation exceeded
Subject undergoing a measure of legal protection (guardianship, supervision