Exploring the Role of the GABAergic Modulation in Pain Transmission in

Status Completed

Clinical Trial Summary

Neuropathic pain affects about 7% of the general population in European countries. Meta-analyses indicate that only a minority of neuropathic pain patients has adequate response to drug therapy and management of neuropathic pain is still an unmet medical need. New insights into the contribution of defined subtypes of GABAA receptors (GABAARs) to the different clinical effects of benzodiazepines, including analgesia, have suggested that α1-sparing selective benzodiazepines, such as N-desmethylclobazam (NDMC), may be a new realistic alternative for the treatment of neuropathic pain. Results from our previous study in healthy volunteers assessing the antihyperalgesic and sedative effects of benzodiazepines on a UVB-induced pain model of central sensitization showed that, at the time of maximum effect, clobazam and clonazepam antihyperalgesic effect was greater than placebo by respectively 15.7% (95% CI 0.8 - 30.5) and 28.6% (95% CI 4.5 - 52.6), p<0.05. Moreover difference in sedation (VAS), as compared to placebo, was only significant for clonazepam 26.3mm (95%CI 15.0-37.7), p<0.001. Our preclinical data also demonstrate that, in recombinant receptors, NDMC has a better α2- over α1GABAARs activity ratio than clobazam and diazepam. And, unlike diazepam, NDMC caused no or modest sedation at antihyperalgesic doses in two strains of wild-type mice. In addition NDMC α2/α1 in vitro activity profile and long term clinical experience from its marketed parent compound (clobazam) make it an advisable clinical candidate for further proof-of-concept assessments in human. Therefore the Geneva University Hospitals have manufactured a new chemical entity and initiated a drug development program for NDMC starting with this proof-of-concept phase 1b randomized double-blind crossover (4 arms) study that will assess the analgesic and sedative effects of NDMC 20mg and 60mg compared to clonazepam 1.5 mg or placebo on a UVB-induced erythema pain model in healthy volunteers.

Clinical Trial Description

n/a

Study Design

Related Conditions & MeSH terms

Clinical Trial Details

NCT number	NCT03375034
Study type	Interventional
Source	University Hospital, Geneva
Contact
Status	Completed
Phase	Phase 1
Start date	March 30, 2017
Completion date	January 31, 2018

View Details

See also
Status	Clinical Trial	Phase
Recruiting	`NCT04699734` - Peripheral Nerve Block in Patients With Painful Diabetic Polyneuropathy	N/A
Recruiting	`NCT06019325` - Rhomboid Intercostal Plane Block on Chronic Pain Incidence and Acute Pain Scores After Mastectomy	N/A
Completed	`NCT05235191` - Effectiveness and Safety of Methadone Versus Placebo for the Control of Neuropathic Pain in Different Etiologies	Phase 3
Completed	`NCT05845177` - Persistent Pain After Hip Replacement
Completed	`NCT05496205` - A SAD Study to Evaluate the Safety, Tolerability and PK/PD of iN1011-N17 in Healthy Volunteers	Phase 1
Not yet recruiting	`NCT05949554` - Electroencephalographic (EEG) Profils for Patients on Intravenous Ketamine.
Withdrawn	`NCT05052645` - Ear Acupuncture for Neuropathic Pain	N/A
Completed	`NCT02930551` - Neuromas as the Cause of Pain	N/A
Completed	`NCT02866396` - Impact of Pregabalin in Chronic Users vs. a Perioperative Limited Prescription on Oxycodone Requirement
Completed	`NCT02824588` - Working Memory Training for Chronic Neuropathic and Fibromyalgia Pain	N/A
Active, not recruiting	`NCT02560545` - Cannabinoids Effects on the Pain Modulation System	N/A
Enrolling by invitation	`NCT02485795` - Observational Study of the Impact of Genetic Testing on Healthcare Decisions and Care in Interventional Pain Management	N/A
Not yet recruiting	`NCT02246517` - The Effect of N2O on Chronic Neuropathic Pain Patients	Phase 0
Completed	`NCT02099890` - The Effect of Diet on Chronic Inflammation and Related Disorders Following Spinal Cord Injury	Phase 3
Completed	`NCT01946555` - Prospective Longitudinal Observational Study to Evaluate the Clinical Characteristics and Opioids Treatments in Patients With Breakthrough Cancer Pain	N/A
Completed	`NCT01718821` - Assessments on Current Pain Managements in Upper Gastrointestinal Cancer Patients	N/A
Completed	`NCT01884662` - Virtual Walking for Neuropathic Pain in Spinal Cord Injury	N/A
Completed	`NCT01669967` - The Role of Intravenous (IV) Lidocaine in the Management of Chronic Neuropathic Pain of Peripheral Nerve Origin	N/A
Completed	`NCT01201317` - A Study to Investigate the Analgesic Efficacy of AZD2423 Compared With Placebo After 28 Days Treatment in Patients With Painful Diabetic Polyneuropathy	Phase 2
Completed	`NCT01207596` - Evaluating the Efficacy and Safety of Extended Release Hydromorphone (Exalgo) in Patients With Neuropathic Pain	Phase 4

Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.

Exploring the Role of the GABAergic Modulation in Pain Transmission in Human — NDMC-101

Clinical Trial Summary

Clinical Trial Description

Study Design

Related Conditions & MeSH terms