NCT06596681

A Study of the Safety and Tolerability of GA in the Treatment of Patients With Refractory Neuropathic Pain

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Sponsor: Beijing Tiantan Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

Previous studies have shown that the anterior cingulate cortex is involved in the regulation of pain and its associated negative emotions, that pyramidal neurons are highly excitable in chronic neuropathic pain conditions, and that silencing of pyramidal neurons can eliminate pain. The aim of this study was to evaluate the safety, tolerability, and efficacy of intracranial injection of GA (containing the hM4Di gene) in the anterior cingulate cortex in combination with oral clozapine for the treatment of refractory neuropathic pain.

Detailed description

There is no effective treatment for refractory neuropathic pain, and this study aims to develop new treatments. Previous studies have shown that the anterior cingulate cortex is involved in the regulation of pain and its associated negative emotions, that pyramidal neurons are highly excitable in chronic neuropathic pain conditions, and that silencing of pyramidal neurons can eliminate pain. Animal studies have shown that inhibition of anterior cingulate cortex neurons using chemical genetics can effectively eliminate pain responses. Our team has obtained similar therapeutic effects with chemical genetics in mouse models of central pain, bone cancer pain, migraine, and nerve injury. In this study, a chemogenetic approach was used to express designer receptors exclusively activated by designer drug (hM4Di) in the anterior cingulate cortex, which binds to clozapine to inhibit neuronal excitability. The aim of this study was to evaluate the safety, tolerability, and efficacy of intracranial injection of GA (containing the hM4Di gene) in the anterior cingulate cortex in combination with oral clozapine for the treatment of refractory neuropathic pain.

Conditions

• Pain, Intractable

Interventions

Type	Name	Description
GENETIC	GA+clozapine	Patients were first given intracranial injections of GA and observed for 14-28 days, followed by a dose-climbing trial of clozapine medication, and finally, after the investigators had determined an effective dose of clozapine, the patients were given a fixed dose of clozapine orally for three months.

Timeline

• Start date: 2024-09-11
• Primary completion: 2026-03-31
• Completion: 2026-06-30
• First posted: 2024-09-19
• Last updated: 2026-01-22

Locations

1 site across 1 country: China