NCT06596681招募中1 期
A Study of the Safety and Tolerability of GA in the Treatment of Patients With Refractory Neuropathic Pain
Beijing Tiantan Hospital1 个研究点 分布在 1 个国家目标入组 6 人开始时间: 2024年9月11日最近更新:
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Incidence and severity of adverse events (AE)/serious adverse events (SAE) as assessed by CTCAE v5.0
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- •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
- •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
- •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
- •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
- •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
研究组 & 干预措施
GA intracranial injection combined with oral clozapine
Experimental
Patients were first given intracranial injections of GA , followed by the oral clozapine.
干预措施: GA+clozapine (Genetic)
结局指标
主要结局
Incidence and severity of adverse events (AE)/serious adverse events (SAE) as assessed by CTCAE v5.0
时间窗: up to 28 weeks
Patient-Reported Adverse Events, Abnormalities on Physical Examination, and Abnormalities in Laboratory Tests
次要结局
- effectiveness: the pain improvement was assessed by Brief pain inventory (BPI) scale.(Weeks 4, 8, and 12 of the effectiveness observation period)
- effectiveness: the sleep quality improvement was assessed by Daily Sleep Interference Scale (DSIS).(Up to 28 weeks)
- effectiveness: the depression improvement was assessed by Hamilton depression (HAMD) scale.(Weeks 4, 8, and 12 of the effectiveness observation period)
- effectiveness: the anxiety improvement was assessed by Hamilton anxiety (HAMA) scale.(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).(Weeks 4, 8, and 12 of the effectiveness observation period)
- Antigen-specific T-cell responses(Up to 28 weeks)
- effectiveness: the degree of pain improvement was assessed by visual analogue scale (VAS).(Weeks 4, 8, and 12 of the effectiveness observation period)
- effectiveness: the degree of sleep quality improvement was assessed by Insomnia Severity Index (ISI).(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).(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).(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).(Weeks 4, 8, and 12 of the effectiveness observation period)
- immunogenicity endpoint: AAV antibody titres(up to 28 weeks)
- Pharmacokinetic profile: Carrier genome levels in urine, blood, tears, nasal secretions(up to 28 weeks)
研究者
yilong Wang
chief physician, professor
Beijing Tiantan Hospital
研究点 (1)
Loading locations...
相似试验
已完成
不适用
Anterior Insula Regulation and Pain EmpathyAnterior Insula Activity During RegulationEmpathic Responses After Anterior Insula RegulationNCT02463981University of Electronic Science and Technology of China37
招募中
不适用
Offset Mechanisms in Evaluation of Lumbar Medial Branch BlocksPain, ProceduralPain, ChronicAnalgesiaFacet Joint PainNCT05961800University of Pittsburgh40
招募中
Unknown
Investigating the effect of adding pain neuroscience education to stabilization exercises using a flexi-bar on pain, disability, abdominal and multifidus muscles geometry in patients with chronic non-specific low back pain.ow back pain.Low back painM54.5IRCT20230505058095N1Shiraz University of Medical Sciences52
已完成
3 期
Effects of GABA-a-Agonists on Pain Mechanisms: An Experimental Study in Healthy VolunteersPainNCT01011036Insel Gruppe AG, University Hospital Bern17
已完成
不适用
Comparison of Ultrasound-Guided Quadratus Lumborum Plane Block and External Oblique Intercostal Plane Block for Postoperative Analgesia After Laparoscopic Cholecystectomy: a Two-Center Randomized Controlled TrialLaparoscopic CholecystectomyNCT06666231Saglik Bilimleri Universitesi Gazi Yasargil Training and Research Hospital46