Effects of GABA-a-Agonists on Pain Mechanisms: An Experimental Study in Healthy Volunteers

Pain Clinical Trial

Official title:

Effects of Gaba-a-Agonists on Pain Mechanisms: An Experimental Study in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01011036
• Other study ID #: 152/09
• Secondary ID: SNF SPUM no.33CM
• Status: Completed
• Phase: Phase 3
• First received: November 6, 2009
• Last updated: August 10, 2010
• Start date: December 2009
• Est. completion date: June 2010

Study information

• Verified date: August 2010
• Source: University Hospital Inselspital, Berne
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: EthikkommissionSwitzerland: Swissmedic
• Study type: Interventional

Clinical Trial Summary

The investigators will use an intradermal capsaicin injection in the forearm to induce a state of localized pain. This localized pain will be measured by different means, and analysed locally and distally by so called quantitative sensory testing. The primary endpoint of measure is the difference in pain perception with and without benzodiazepines/GABA-Agonists around the injection point of capsaicin. The secondary endpoints are to measure pain modulation locally and distally by different quantitative tests as electricity, pressure pain thresholds, and ice water tests.

The investigators' hypothesis is that clobazam induces higher pain thresholds as placebo and less sedation than the control medication clonazepam.

Description:

Background

Neuropathic and nociceptive pain are linked to plastic changes of the central nervous system. These lead to lower pain thresholds. An important component of this neuronal plasticity is a diminished inhibition-control of the neurons on the level of the spine, where an alpha-3 subunit of the glycine receptor plays an important role. Modulation of this receptor subunit with specific and non-specific GABA-Agonists produce antinociception. The new fact is, that a subunit specific medication does not induce sedation in animals. The relationship of pain modulation and Gaba-Agonists is not well studied in humans. The benzodiazepine used in pain therapy in humans is clonazepam, which induces a strong sedation, reason why it is not much used in a chronic pain setting. Clobazam is another GABA-Agonist, which is less sedative. To our knowledge its effects on pain modulation has never been studied in humans.

Objective

The aim is an analysis and description of clobazam on the central pain mechanisms. We will use well known quantitative sensory testing methods therefore.

The primary objective is to gather data about potential clinical use of clobazam in pain therapy. The secondary aim would be to do the same tests on new specific alpha-3 agonists, which are being developed by pharmaceutical industry.

Methods

Quantitative sensory testing is being made after eliciting an area of hyperalgesia on the forearm by capsaicin.

The area of hyperalgesia around the injection point will be the primary issue of this study.

The medication given to our patients will be a cross-over, double blind randomized administration of clobazam, clonazepam (positive control) and tolterodine (active placebo). Quantitative sensory testing will be made before and after study medication administration.

The quantitative sensory testing consists of the area of hyperalgesia around capsaicin injection point, pressure pain elicited with an electronic pressure algometer, ice-water testing of the hand, single and multiple electrical skin and muscle stimulation, pressure-cuff algometry and the side effects of the administered medication with psychomotor testing.

Before we start the study protocol each patient will have a blood sample drawn for genetic testing of the different cytochrome subunits (CYP P450 2C19, 3A4).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: June 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• European males

• 18-55 years old

• non smoking status or less than 10 cigarettes per day

• no disease

Exclusion Criteria

• any medication

• any drug abuse

• diseases of any type

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pain

Intervention

Drug:
• clobazam
test substance
• clonazepam
positive control
• tolterodine
active placebo

Locations

Country	Name	City	State
Switzerland	Dep of Anesthesiology and Pain Therapy, University Hospital Bern	Bern

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	area of hyperalgesia on the forearm		11.2010	No
Secondary	Diffuse noxious inhibition control		11.2010	No
Secondary	Pressure cuff algometry		11.2010	No
Secondary	pressure pain		11.2010	No
Secondary	electrical stimulation-temporal summation		11.2010	No
Secondary	psychomotor testing		11.2010	No
Secondary	Pharmacokinetic study: plasmatic concentration measured in regular intervals with blood samples, starting at time zero and ending at time plus 24h after drug administration.		11.2010	No
Secondary	Pharmacodynamic study: Measurement of pharmacodynamic behaviour of our 3 tested substances in relation to sedation score.		11.2010	No
Secondary	Pharmacogenetic study: Measurement of subtype cytochrome P450 CYP3A4 and CYP2C19 by metabolites of midazolam and omeprazol. Genotyping of cytochrome P450 CYP3A4 and CYP 2C19.		11.2010	No