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Pain, IntractableEarly Phase 1NCT06596681

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

A Early Phase 1 study testing GA+clozapine in people with Pain, Intractable, run by Beijing Tiantan Hospital at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Pain, Intractable
What is being tested?
GA+clozapine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteChina
Study dates
11 Sep 2024to 31 Dec 2026
Phase
Early Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • Regularised treatment with conventional medical therapy (including, but not limited to, medication, physiotherapy, cognitive therapy, nerve blocks and other non-invasive or minimally invasive treatments) for at least 3 months with no symptomatic relief or emergence of tolerance, as assessed by the investigator
  • Pharmacological treatment means a full course of treatment with at least two first-line medications, as assessed by the investigator
  • Mean visual analogue scale (VAS) value ≥4 cm and/or mean numerical rating scale (NRS) value ≥4 points within one week of baseline at enrolment
  • Subjects who have had a stable analgesic regimen for at least 30 days prior to the intensity of pain described in Inclusion Criterion 2 and agree not to arbitrarily change the type and dose of medication that they are currently taking until the end of the period of assessment of the effectiveness of this trial, as assessed by the investigator
  • Subjects volunteered to participate in the trial and gave fully informed consent to sign an informed consent form
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  • Have stable neurological status as assessed by the researcher through motor, sensory and reflex functions
  • Subjects are considered reliable and able to comply with the trial protocol (e.g., able to understand and complete relevant scales), visit protocols, and medication administration, according to the investigator's judgement
  • Subjects of childbearing potential agree to sign an informed consent form and have no plans to have children during the study period and voluntarily use effective contraception (oral contraceptives are prohibited) and do not plan to donate sperm or eggs

Who cannot join

  • 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:
  • suffering from severe cardiopulmonary disease such as unstable angina, myocardial infarction, severe arrhythmia, recurrent asthma attacks, etc;
  • Malignant tumours of the central nervous system or other systems. 4.Current status such as coagulation disorders, bleeding tendencies, platelet dysfunction, severely reduced function due to underlying cardiac/pulmonary disease, progressive peripheral vascular disease, or poorly controlled diabetes mellitus, and subjects who may be suffering from a relevant disease state that affects surgery as assessed by the investigator 5.Currently on anticoagulants and unable to stop them 6.Localised infection or active systemic infection at the anticipated surgical access site 7.History of previous intracranial surgical treatment (except for minimally invasive paracentesis for diagnostic tests, etc.) 8.Patients with severe psychiatric symptoms (e.g., major depression, schizophrenia, etc.) or significant suicidal tendencies or assessed by the investigator to be unable to complete the clinical trial 9. Pre-existing or concomitant severe hepatic dysfunction, renal dysfunction, cardiac dysfunction (in which severe hepatic dysfunction is defined as ALT ≥ 2.0 times the upper limit of normal or AST ≥ 2.0 times the upper limit of normal; severe renal dysfunction refers to a CRE ≥ 1.5 times the upper limit of normal or an eGFR < 40mL/min/1.73m2; and severe cardiac dysfunction refers to an NYHA score of grade 3-4) ，delirium, hypotension, epilepsy, glaucoma, myelosuppression or leukopenia, severe central nervous system depression, or coma from any cause 10. Subjects with abnormal laboratory test values:
  • <!-- -->
  • white blood cell count <3.5 x 109/L and neutrophil count <1.0 x 109/L
  • Platelet (PLT) <75 x 109/L
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  • Coagulation: prothrombin time and activated partial thromboplastin time >1.5 x ULN
  • 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 contraindications 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 investigational 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Yahui Zhu, Doctor contact

13439182912

zhuyahuidr@sina.com

China1 site, 1 recruiting

  • Beijing Tiantan Hospital

    Beijing, Beijing Municipality, 100070

    Zhu Yahui, +8613439182912, zhuyahuidr@sina.com

    Yahui Zhu, Doctor

    Recruiting

Other trials in China

About this study

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.

Read the 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.

Being tested
GA+clozapine
Keywords
Refractory neuropathic pain, GA, clozapine, safety
Medical subject headings
Pain, Intractable, Neuralgia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GA+clozapineGenetic

    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.

Study groups in NCT06596681
Study groupRoleWhat they receive
GA intracranial injection combined with oral clozapineExperimentalPatients were first given intracranial injections of GA , followed by the oral clozapine.
Receives: Genetic: GA+clozapine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: up to 28 weeks

Secondary outcomes (13)

  1. 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.

    Measured: Weeks 4, 8, and 12 of the effectiveness observation period

  2. 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.

    Measured: Weeks 4, 8, and 12 of the effectiveness observation period

  3. 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.

    Measured: Weeks 4, 8, and 12 of the effectiveness observation period

  4. 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.

    Measured: Up to 28 weeks

  5. 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.

    Measured: Weeks 4, 8, and 12 of the effectiveness observation period

  6. 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.

    Measured: Weeks 4, 8, and 12 of the effectiveness observation period

  7. 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).

    Measured: Weeks 4, 8, and 12 of the effectiveness observation period

  8. 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.

    Measured: Weeks 4, 8, and 12 of the effectiveness observation period

  9. 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'.

    Measured: Weeks 4, 8, and 12 of the effectiveness observation period

  10. 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.

    Measured: Weeks 4, 8, and 12 of the effectiveness observation period

  11. immunogenicity endpoint: AAV antibody titres

    Use of specific antibodies for AAV antibody titre testing

    Measured: up to 28 weeks

  12. Antigen-specific T-cell responses

    Antigen-specific T-cell responses

    Measured: Up to 28 weeks

  13. Pharmacokinetic profile: Carrier genome levels in urine, blood, tears, nasal secretions

    Carrier genome levels in urine, blood, tears, nasal secretions

    Measured: up to 28 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2024
  2. Study start11 Sep 2024
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
A group of patients with refractory neuropathic pain
Masking
None (open label)
Enrolment
6 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06596681
Sponsor's protocol ID
KY2024-157-03
Status last verified
Jul 2026
First submitted
27 Aug 2024
Last updated
31 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing GA+clozapine in people with Pain, Intractable, run by Beijing Tiantan Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Yahui Zhu, Doctor (13439182912, zhuyahuidr@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence and severity of adverse events (AE)/serious adverse events (SAE) as assessed by CTCAE v5.0 (time frame: up to 28 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06596681.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.

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