Dextromethorphan Effect on Central Sensitization to Pain in Healthy Volunteers

NCT02596360 | Completed Phase 1

• 2 other identifiers: CHU-02482015-003271-30
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Experimental Pain; Hyperalgesia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• 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).

Study Arms (2)

Dextromethorphan

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Pulmodexane® 30mg DRUG

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).

Dextromethorphan

lactose DRUG

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

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• Medical and surgical history incompatible with the study
• 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

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead

Study Sites (1)

CHU Clermont-Ferrand

Clermont-Ferrand, 63003, France

Location

MeSH Terms

Conditions

Hyperalgesia

Interventions

Lactose

Condition Hierarchy (Ancestors)

Somatosensory Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Study Officials

• Gisèle PICKERING

  University Hospital, Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2015
• First Posted: November 4, 2015
• Study Start: November 1, 2015
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: April 1, 2016

Record last verified: 2016-03

Locations

FR (1)