Back to results

Dextromethorphan Effect on Central Sensitization to Pain in Healthy Volunteers (Hydex)

Primary Purpose

Experimental Pain, Hyperalgesia

Status

Completed

Phase

Phase 1

Locations

France

Study Type

Interventional

Intervention

Pulmodexane® 30mg

lactose

About this trial

This is an interventional treatment trial for Experimental Pain focused on measuring Antinociception, Freeze-induced hyperalgesia model, Dextromethorphan, NMDA-receptors, Pharmacogenetic, CYP3A4 gene, MDR1 gene

Eligibility Criteria

18 Years - 45 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

CHU Clermont-Ferrand

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Dextromethorphan

Placebo

Arm Description

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).

Outcomes

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)

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)

Percentage changes in mechanical pain thresholds (MPT) using electronic von frey in control skin zone (Z0)

Percentage changes in mechanical pain thresholds (MPT) using electronic von frey in primary hyperalgesic zone (Z1)

Conditioned Pain Modulation (CPM) assessment

Reaction time assessment using RTI CANTAB® test

Determination of potential central effects of dextromethorphan measuring pupillary reaction

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

Dosage of plasma concentration of dextromethorphan and dextromethorphan's metabolites from blood collections

Full Information

NCT ID

NCT02596360

First Posted

October 19, 2015

Last Updated

March 31, 2016

Sponsor

University Hospital, Clermont-Ferrand

1. Study Identification

Unique Protocol Identification Number

NCT02596360

Brief Title

Dextromethorphan Effect on Central Sensitization to Pain in Healthy Volunteers

Acronym

Hydex

Official Title

Dextromethorphan Effect on Central Sensitization to Pain in Healthy Volunteers

Study Type

Interventional

2. Study Status

Record Verification Date

March 2016

Overall Recruitment Status

Completed

Study Start Date

November 2015 (undefined)

Primary Completion Date

March 2016 (Actual)

Study Completion Date

March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Clermont-Ferrand

4. Oversight

5. Study Description

Brief Summary

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

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Experimental Pain, Hyperalgesia

Keywords

Antinociception, Freeze-induced hyperalgesia model, Dextromethorphan, NMDA-receptors, Pharmacogenetic, CYP3A4 gene, MDR1 gene

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dextromethorphan

Arm Type

Experimental

Arm Description

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 Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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).

Intervention Type

Drug

Intervention Name(s)

Pulmodexane® 30mg

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

lactose

Intervention Description

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).

Primary Outcome Measure Information:

Title

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).

Secondary Outcome Measure Information:

Title

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

Title

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).

Title

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).

Title

Conditioned Pain Modulation (CPM) assessment

Time Frame

at Day -1 before treatment and Day 0 30 min before treatment (T0-30min)

Title

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).

Title

Determination of potential central effects of dextromethorphan measuring pupillary reaction

Description

Time Frame

Title

Study of genetic polymorphism of cytochrome P450 3A4 and genetic polymorphism of MDR1 gene

Time Frame

up to 6 months.

Title

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).

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gisèle PICKERING

Organizational Affiliation

University Hospital, Clermont-Ferrand

Official's Role

Principal Investigator

Facility Information:

Facility Name

CHU Clermont-Ferrand

City

Clermont-Ferrand

ZIP/Postal Code

63003

Country

France

12. IPD Sharing Statement

Learn more about this trial

Dextromethorphan Effect on Central Sensitization to Pain in Healthy Volunteers

We'll reach out to this number within 24 hrs