An Early Phase 1 interventional study of GA+clozapine in Pain, Intractable, sponsored by Beijing Tiantan Hospital. Recruiting at 1 site in China. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-07-31.
Sponsored by Beijing Tiantan Hospital · Early Phase 1, Interventional, and Treatment
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.
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.
90 studies on the registry are indexed under Pain, Intractable; 16 are open to participants now.
This study's planned enrollment of 6 is below the median of 60 across 64 interventional studies indexed under Pain, Intractable.
Browse Pain, Intractable studies →Beijing Tiantan Hospital is the lead sponsor of 489 studies on the registry; 293 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients with a definitive diagnosis of neuropathic pain, including but not limited to painful diabetic peripheral neuropathy, trigeminal neuralgia, and post-stroke pain, aged 18-65 years old (regardless of gender), with:
Exclusion Criteria:
1.In patients with painful diabetic peripheral neuropathy, amputation due to diabetes mellitus or large (≥3cm) and/or gangrenous ulcers on the lower limbs 2.Currently diagnosed with progressive neurological disorders such as multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, tumours of the brain or spinal cord, and neurodegenerative disorders, as determined by the investigators 3.Have a chronic systemic disease that, as assessed by the investigator, may affect the subject's participation in the study, including but not limited to:
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Blood adeno-associated virus (AAV) antibody titre >1:1000 11.Patients taking drugs that cause granulocyte deficiency or have myelosuppressive effects 12.Patients with granulocyte deficiency or severe granulocytopenia due to prior clozapine use 13.Patients with and/or allergies to medications during the trial (e.g. clozapine or other components of clozapine, contrast agents, etc.) 14.Have gastrointestinal diseases (Crohn's disease, acute or chronic pancreatitis, paralytic intestinal obstruction, etc.) or major gastrointestinal surgeries that affect the absorption, metabolism and excretion of drugs, etc.
15.Subjects had received any gene or cellular therapy 16. Known history of alcohol, drug abuse 17.Patients participating in other clinical trials or applying other biologics, drugs or devices within six months prior to screening 18.Contraindications to MRI and functional MRI (e.g. claustrophobia, metallic foreign bodies in the body) 19.Clozapine-related serious adverse reactions are considered a screening failure if they occur during the screening period, at the judgement of the investigator
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients were first given intracranial injections of GA , followed by the oral clozapine.
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.
Incidence and severity of adverse events (AE)/serious adverse events (SAE) as assessed by CTCAE v5.0
Patient-Reported Adverse Events, Abnormalities on Physical Examination, and Abnormalities in Laboratory Tests
Time frame: up to 28 weeks
effectiveness: the degree of pain improvement was assessed by visual analogue scale (VAS).
The degree of pain improvement was assessed by visual analogue scale (VAS). VAS Score: i.e. Pain Scale Rating, which assesses the severity of pain using visual analogue methods. The scale uses a 10cm long straight line with '0' cm and '10' cm at each end, with 0 indicating no pain and 10 indicating unbearable severe pain.
Time frame: Weeks 4, 8, and 12 of the effectiveness observation period
effectiveness: the pain improvement was assessed by Brief pain inventory (BPI) scale.
the pain improvement was assessed by Brief pain inventory (BPI) scale. BPI: Evaluates pain severity and functional interference. Part 1 (Severity): Current pain, average pain (24h), worst pain (24h), least pain (24h), pain relief from treatments. Part 2 (Interference): Impact on general activity, mood, walking ability, work, relationships, sleep, and enjoyment of life.
Time frame: Weeks 4, 8, and 12 of the effectiveness observation period
effectiveness: the degree of sleep quality improvement was assessed by Insomnia Severity Index (ISI).
The degree of sleep quality improvement was assessed by Insomnia Severity Index (ISI). ISI scale: 7 entries, each rated 0-4. The total score ranges from 0-28, and the higher the score the greater the severity of insomnia.
Time frame: Weeks 4, 8, and 12 of the effectiveness observation period
effectiveness: the sleep quality improvement was assessed by Daily Sleep Interference Scale (DSIS).
the sleep quality improvement was assessed by Daily Sleep Interference Scale (DSIS). DSIS: An 11-point Likert scale ranging from 0 ("Pain did not interfere with sleep") to 10 ("Pain completely interfered with sleep" \[inability to sleep due to pain\]). Subjects will recall sleep interference over the preceding 24 hours each morning and record scores.
Time frame: Up to 28 weeks
effectiveness: the depression improvement was assessed by Hamilton depression (HAMD) scale.
The depression improvement was assessed by Hamilton depression (HAMD) scale. HAMD: 17-item version implemented in this protocol. Trained raters will conduct combined evaluations through structured interviews and behavioral observations.
Time frame: Weeks 4, 8, and 12 of the effectiveness observation period
effectiveness: the degree of depression improvement was assessed by Patient Health Questionnaire-9 (PHQ-9).
The degree of depression improvement was assessed by Patient Health Questionnaire-9 (PHQ-9).PHQ-9: Used to screen patients for depressive disorders. The PHQ-9 scale has 9 items, each of which is a 4-point scale from 0-3. According to the scale, the PHQ-9 score is divided into 5 groups: 0-4, 5-9, 10-14, 15-19, and 20-27, corresponding to no, mild, moderate, moderately severe, and severe depression, respectively.
Time frame: Weeks 4, 8, and 12 of the effectiveness observation period
effectiveness: the anxiety improvement was assessed by Hamilton anxiety (HAMA) scale.
The anxiety improvement was assessed by Hamilton anxiety (HAMA) scale. HAMA: 14-item clinician-administered scale recognized as a primary diagnostic tool for anxiety disorders according to the Chinese Classification of Mental Disorders-3 (CCMD-3).
Time frame: Weeks 4, 8, and 12 of the effectiveness observation period
effectiveness: the degree of anxiety improvement was assessed by Generalized Anxiexy Disorde-7 (GAD-9).
The degree of anxiety improvement was assessed by Generalized Anxiexy Disorde-7 (GAD-9). The GAD-7 is a widely used self-assessment scale for anxiety symptoms that has been used in recent years to screen not only for anxiety disorders, but also for panic disorder, social anxiety disorder, and post-traumatic stress disorder. The scale consists of 7 items that rate tension, uncontrollable worry, excessive worry, inability to relax, inability to sit still, irritability, and feelings of foreboding. The number of days in the last 2 weeks that the target symptom was present was assessed: 0 for no symptoms, 1 for a few days, 2 for more than half of the days, and 3 for almost every day. A total score of 5 to 9 is considered mild, 10 to 14 is moderate, and 15 to 21 is severe.
Time frame: Weeks 4, 8, and 12 of the effectiveness observation period
effectiveness: the degree of quality of life improvement was assessed by EuroQOL, 5 Domains, 5 Levels (EQ-5D-5L).
The degree of quality of life improvement was assessed by EuroQOL, 5 Domains, 5 Levels (EQ-5D-5L). The EQ-5D-5L is a set of standardised scales to measure health status. The EQ-5D-5L consists of two parts, the EQ-5D-5L Health Descriptor System and the EQ-VAS. The EQ-5D-5L Health Descriptor System describes five dimensions: mobility, Self-Care, Usual Activities, Pain/Comfort, Anxiety/Depression. Each dimension consists of five levels: 1 No difficulty, 2 Some difficulty, 3 Moderate difficulty, 4 Severe difficulty, and 5 Unable to perform/very severe difficulty. Responses to the five dimensions generate a five-digit code describing the state of health, with a state of health of 11111 indicating no problems on any of the five dimensions.The EQ-VAS records the self-assessed state of health on a vertical, visually analogue scale, with the ends of the scale labelled 'the best health you can imagine' and 'the worst health you can imagine'.
Time frame: Weeks 4, 8, and 12 of the effectiveness observation period
effectiveness: the quality of life improvement was assessed by Patient global impression of change (PGIC).
the quality of life improvement was assessed by Patient global impression of change (PGIC). PGIC: A 7-point scale assessing subjects' overall perception changes following treatment: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; 7 = Very much worse.
Time frame: Weeks 4, 8, and 12 of the effectiveness observation period
immunogenicity endpoint: AAV antibody titres
Use of specific antibodies for AAV antibody titre testing
Time frame: up to 28 weeks
Antigen-specific T-cell responses
Antigen-specific T-cell responses
Time frame: Up to 28 weeks
Pharmacokinetic profile: Carrier genome levels in urine, blood, tears, nasal secretions
Carrier genome levels in urine, blood, tears, nasal secretions
Time frame: up to 28 weeks
fMRI: Neuronal activation in ACC brain regions and connectivity of ACC brain regions with other brain regions
fMRI: is a radiation-free, non-invasive functional imaging technique that detects the level of neuronal activation in brain tissue by probing blood oxygen saturation and water levels in brain tissue. In this programme, local brain activity (activation of neurons in brain regions) and brain integration (functional connectivity between brain regions) are assessed, especially in the ACC brain region.
Time frame: up to 28 weeks
Drug Dose Reduction
After the patient is treated with GA intracranial injections combined with oral clozapine and the pain symptoms improve, the previous analgesic medication of patients may be considered to be gradually tapered off
Time frame: up to 28 weeks
Plan to share: No
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