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

August 10, 2010 updated by: University Hospital Inselspital, Berne

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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).

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Bern, Switzerland, 3010
        • Dep of Anesthesiology and Pain Therapy, University Hospital Bern

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 1
Drug: clobazam
test substance
Drug: clonazepam
positive control
Drug: tolterodine
active placebo
Other: 2
Drug: clobazam
test substance
Drug: clonazepam
positive control
Drug: tolterodine
active placebo
Other: 3
Drug: clobazam
test substance
Drug: clonazepam
positive control
Drug: tolterodine
active placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
area of hyperalgesia on the forearm
Time Frame: 11.2010
11.2010

Secondary Outcome Measures

Outcome Measure
Time Frame
Diffuse noxious inhibition control
Time Frame: 11.2010
11.2010
Pressure cuff algometry
Time Frame: 11.2010
11.2010
pressure pain
Time Frame: 11.2010
11.2010
electrical stimulation-temporal summation
Time Frame: 11.2010
11.2010
psychomotor testing
Time Frame: 11.2010
11.2010
Pharmacokinetic study: plasmatic concentration measured in regular intervals with blood samples, starting at time zero and ending at time plus 24h after drug administration.
Time Frame: 11.2010
11.2010
Pharmacodynamic study: Measurement of pharmacodynamic behaviour of our 3 tested substances in relation to sedation score.
Time Frame: 11.2010
11.2010
Pharmacogenetic study: Measurement of subtype cytochrome P450 CYP3A4 and CYP2C19 by metabolites of midazolam and omeprazol. Genotyping of cytochrome P450 CYP3A4 and CYP 2C19.
Time Frame: 11.2010
11.2010

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Inselspital, Berne

Investigators

  • Study Director: Michele Curatolo, Professor, University of Bern
  • Principal Investigator: Pascal H Vuilleumier, Dr med, University of Bern

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2009

Primary Completion (Actual)

April 1, 2010

Study Completion (Actual)

June 1, 2010

Study Registration Dates

First Submitted

November 6, 2009

First Submitted That Met QC Criteria

November 10, 2009

First Posted (Estimate)

November 11, 2009

Study Record Updates

Last Update Posted (Estimate)

August 11, 2010

Last Update Submitted That Met QC Criteria

August 10, 2010

Last Verified

August 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 152/09
  • SNF SPUM no.33CM30_124117

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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