Safety and Tolerability Study of GA Gene Therapy Combined with Oral Clozapine for Adults With Hard-to-Treat Neuropathic Pain

What this Trial Is About

Researchers are investigating a new treatment for people with refractory neuropathic pain, a condition where traditional therapies have failed to relieve pain. The study focuses on the anterior cingulate cortex, a brain area involved in pain and negative emotions. Previous research showed that silencing certain neurons in this area can reduce pain, and this trial aims to test the safety and effects of injecting a gene therapy called GA, combined with oral clozapine medication, for this purpose. Participants will first receive an intracranial injection of GA, which contains a gene hM4Di designed to reduce neuron excitability when activated by clozapine. After injection, there is an observation period of 14 to 28 days, followed by a dose-escalation phase where clozapine doses are gradually increased. Once an effective dose is identified, participants will take a fixed oral dose of clozapine for three months. This approach uses a chemogenetic method to inhibit brain neurons related to pain. Throughout the study, participants will be closely monitored for safety by checking for adverse events up to 28 weeks. Effectiveness will be measured at weeks 4, 8, and 12 using various tools to assess pain levels, sleep quality, depression, anxiety, and quality of life. Additional tests include immune response markers and pharmacokinetic profiles. Participants must follow the study protocol, attend visits, and complete assessments for up to 28 weeks.

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