PainPhase 3NCT01011036
Effects of GABA-a-Agonists on Pain Mechanisms: An Experimental Study in Healthy Volunteers
A Phase 3 study testing clobazam, clonazepam and tolterodine in people with Pain, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
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. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Pain
- What is being tested?
- clobazam, clonazepam and tolterodine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteSwitzerland
- Study dates
- Dec 2009to Jun 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- European males
- 18-55 years old
- non smoking status or less than 10 cigarettes per day
- no disease
Who cannot join
- any medication
- any drug abuse
- diseases of any type
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Dep of Anesthesiology and Pain Therapy, University Hospital Bern
Bern, 3010
About this study
Official title: 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.
Read the 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).
- Conditions
- Pain
- Being tested
- clobazam, clonazepam, tolterodine
- Keywords
- healthy study subjects, no disease
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
clobazamDrug
test substance
clonazepamDrug
positive control
tolterodineDrug
active placebo
| Study group | Role | What they receive |
|---|---|---|
| 1 | Other | Not described Receives: Drug: clobazam; Drug: clonazepam; Drug: tolterodine |
| 2 | Other | Not described Receives: Drug: clobazam; Drug: clonazepam; Drug: tolterodine |
| 3 | Other | Not described Receives: Drug: clobazam; Drug: clonazepam; Drug: tolterodine |
What is being measured
The primary outcome is the main question the study is designed to answer.
area of hyperalgesia on the forearm
Measured: 11.2010
Secondary outcomes (8)
Diffuse noxious inhibition control
Measured: 11.2010
Pressure cuff algometry
Measured: 11.2010
pressure pain
Measured: 11.2010
electrical stimulation-temporal summation
Measured: 11.2010
psychomotor testing
Measured: 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.
Measured: 11.2010
Pharmacodynamic study: Measurement of pharmacodynamic behaviour of our 3 tested substances in relation to sedation score.
Measured: 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.
Measured: 11.2010
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2009 (estimated)
- Study startDec 2009
- Primary completionApr 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PainStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Investigators
- Michele Curatolo, Professor, Study director, University of BernPascal H Vuilleumier, Dr med, Principal investigator, University of Bern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01011036
- Sponsor's protocol ID
- 152/09
- Other IDs
- SNF SPUM no.33CM30_124117
- Status last verified
- Aug 2010
- First submitted
- 6 Nov 2009
- Last updated
- 11 Aug 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Vuilleumier PH, Besson M, Desmeules J, Arendt-Nielsen L, Curatolo M. Evaluation of anti-hyperalgesic and analgesic effects of two benzodiazepines in human experimental pain: a randomized placebo-controlled study. PLoS One. 2013;8(3):e43896. doi: 10.1371/journal.pone.0043896. Epub 2013 Mar 15.
PubMed 23554851
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Gaba-a-Agonists on Pain Mechanisms: An Experimental Study in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01011036
- Acronym / sponsor ID
- 152/09
- Conditions
- Pain
- Keywords
- healthy study subjects, no disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- Dec 2009
- Primary completion
- Apr 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 11 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Other | Drug: clobazam, Drug: clonazepam, Drug: tolterodine |
| 2 | Other | Drug: clobazam, Drug: clonazepam, Drug: tolterodine |
| 3 | Other | Drug: clobazam, Drug: clonazepam, Drug: tolterodine |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- European males
- 18-55 years old
- non smoking status or less than 10 cigarettes per day
- no disease
Key exclusion criteria (3 listed)
- any medication
- any drug abuse
- diseases of any type
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| clobazamtest substance | Drug | 1, 2, 3 |
| clonazepampositive control | Drug | 1, 2, 3 |
| tolterodineactive placebo | Drug | 1, 2, 3 |
Primary outcome
area of hyperalgesia on the forearm
Time frame: 11.2010
8 secondary outcomes
Diffuse noxious inhibition control
Time frame: 11.2010
Pressure cuff algometry
Time frame: 11.2010
pressure pain
Time frame: 11.2010
electrical stimulation-temporal summation
Time frame: 11.2010
psychomotor testing
Time frame: 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
Pharmacodynamic study: Measurement of pharmacodynamic behaviour of our 3 tested substances in relation to sedation score.
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2010.
- Derived from this study: PubMed 23554851Vuilleumier PH, Besson M, Desmeules J, Arendt-Nielsen L, Curatolo M. Evaluation of anti-hyperalgesic and analgesic effects of two benzodiazepines in human experimental pain: a randomized placebo-controlled study. PLoS One. 2013;8(3):e43896. doi: 10.1371/journal.pone.0043896. Epub 2013 Mar 15.
Related trials for Pain
Not yet recruiting
Effect of Stress Ball Use During Femoral Arterial Sheath Removal After Coronary Angiography
Femoral Arterial Sheath Removal, Stress Ball
Recruiting
Empowered Relief® for Cancer Survivors With Chronic Pain
Chronic Pain Due to Cancer, Pain Catastrophizing
RecruitingPhase 4
ESP Blocks for Posterior Spinal Fusion
Postoperative Pain
RecruitingObservational study
Pain Phenotypes in Individuals With Multiple Sclerosis
Multiple Sclerosis, Chronic Pain
Not yet recruiting
Effects of Hip Hinge Exercises on Pain, Range of Motion and Functional Disability in Non-specific Low Back Pain.
Low Back Pain
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michele Curatolo, Professor study director
University of Bern
Pascal H Vuilleumier, Dr med principal investigator
University of Bern
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing clobazam, clonazepam and tolterodine in people with Pain, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Aug 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
area of hyperalgesia on the forearm (time frame: 11.2010). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01011036, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2010.