GABAergic Modulation in Pain Transmission in Human: Effect of the GABAA Agonist Clobazam on Peripheral and Central Sensitisation

NCT01291316 | Completed Phase 1

• 1 other identifier: GABA-SPUM
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

In animal, the GABAergic system modulates central sensitisation, which is a key phenomenon in pain processing. The development of GABAA agonists targeting the subunits of the GABAA receptor implicated in nociception, but not the subunit implicated in sedation is attractive as it opens new perspectives of testing the role of GABAergic modulation of pain processing in human volunteers. The purpose of this subproject is to test the effect of the specific α2 and α3 agonist but sparing α1 effect TPA023 on a human model of peripheral and central sensitisation and to correlate its pharmacodynamic effect with the pharmacokinetic of the compound. The results would contribute to clarify the potential role of these α2/α3 agonist but sparing α1drugs in clinical pain conditions.

Conditions

Neuropathic Pain

Outcome Measures

Primary Outcomes (1)

• Determination of the impact of clobazam on the change in the area of secondary hyperalgesia (in cm2) mapped with a Von Frey filament (256mN).

  3 single days spaced out with at least two weeks wash-out periods

Secondary Outcomes (8)

• Change in the pain threshold (heat (°C) static mechanical (g) and dynamic mechanical (Numerical rating scale NAS) in the area of secondary hyperalgesia

  3 single days spaced out with at least two weeks wash-out periods

• Change in the pain threshold (heat (°C ) static mechanical (g) and dynamic mechanical (NAS)) in the area of primary hyperalgesia

  3 single days spaced out with at least two weeks wash-out periods

• Change in Nociceptive Flexion Reflex

  3 single days spaced out with at least two weeks wash-out periods

• Change in the latency and in the area under the pain intensity/time curve in cold pressor test

  3 single days spaced out with at least two weeks wash-out periods

• Change in mean target saccades peak velocity, target saccades acceleration and deceleration, in saccade latency (msec), in saccadic accuracy, in smooth pursuit lead time and in the number of saccadic intrusions in the smooth pursuit.

  3 single days spaced out with at least two weeks wash-out periods

Study Arms (3)

clobazam

EXPERIMENTAL

Drug: clobazam

clonazepam

ACTIVE COMPARATOR

Drug: Clonazepam

tolterodine

PLACEBO COMPARATOR

Drug: Tolterodine

Interventions

Clonazepam DRUG

clonazepam, 1 mg, single oral dose

clonazepam

Tolterodine DRUG

Tolterodine 1,37mg, single oral dose

tolterodine

clobazam DRUG

clobazam 20 mg, single oral dose

clobazam

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male subject, age between 18 and 60 year old
• Caucasian
• Type 3 skin phototype
• Non smoker or moderate smoker (\< 10 cigarettes/day)
• No clinically abnormal findings on history and/or on physical examination
• Presence of an area of secondary hyperalgesia after UVB irradiation

You may not qualify if:

• Any concomitant illness
• Current or past history of drug and alcohol abuse or current intake of more than 3 glasses of alcohol a day or more than 21 glasses of alcohol per week
• Psychotropic drug intake during the last month
• Sun allergy or any skin disease
• Current and regular intake of any drugs that might affect nociception Paracetamol, or NSAIDS with a short half lives are permitted but should be stopped at least 48 h before the UVB session

Sponsors & Collaborators

• University Hospital, Geneva: lead

Study Sites (1)

University Hospitals

Geneva, 1211, Switzerland

Location

MeSH Terms

Conditions

Neuralgia

Interventions

Clonazepam; Tolterodine Tartrate; Clobazam

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenylpropanolamine; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Cresols; Phenols

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 7, 2011
• First Posted: February 8, 2011
• Study Start: April 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: December 14, 2011

Record last verified: 2011-12

Locations

CH (1)