Efficacy and Safety of Combo-stim Deep Brain Stimulation for Treatment-refractory Mental Disorders: a Multi-center, Single Arm, Prospective, Open-label, Extendable Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- reduce rate of PANSS score compared to baseline after 12 weeks of stimulation
研究概览
简要总结
This is a multi-center, single arm, prospective, open-label, extendable study for the efficacy and safety of combo-stim deep brain stimulation for treatment-refractory mental disorders (obsessive-compulsive disorder, schizophrenia, bipolar with depression, anorexia nervosa, gambling disorder and adult autism).
详细描述
Total of 18 subjects from Shanghai Mental Health Center who fit inclusion and don't fit exclusion criteria are recruited to undergo neurosurgical implantation of combo-stim DBS in bilateral nucleus accumbens (NAcc) and anterior limb of internal capsule (ALIC) on a certain date, the DBS system will be turned on for stimulation and parameters adjusted 7-14 days after implantation, treatment purposes are evaluated after system has been turned on for 8-24 weeks. Primary efficacy is evaluated by change in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Positive and Negative Syndrome (PANSS), Montgomery-Asberg Depression Rating Scale (MADRS), Body Mass Index (BMI), Autism Behavior Checklist (AuBC) score and longest consecutive days without gambling within one month. Safety is evaluated by adverse events (AE) and device-related adverse events (ADE), serious adverse events (SAE) and serious device-related events (SADE), device deficiencies (DD) and device malfunction, physical examination and vital signs, laboratory examination, electrocardiogram (ECG), imaging examination, scale evaluation and early drop out ratio due to AE.
Recruitment Progress Update (As of August 2026)
This ongoing study has completed a total of 16 screenings and enrolled 15 participants. Detailed recruitment and safety status by indication is presented below:
- Obsessive-Compulsive Disorder (OCD) A total of 5 participants were screened, 4 participants were enrolled, and 1 participant failed screening. All 4 enrolled participants have completed study discontinuation.
- Bipolar Disorder A total of 6 participants were screened and all 6 participants were successfully enrolled with no screening failure. Among the enrolled participants, 5 participants have discontinued from the study, and 1 serious adverse event (SAE) has been reported in this subgroup.
- Schizophrenia Spectrum Disorder A total of 3 participants were screened and enrolled, with no screening failure. Two participants have discontinued from the study.
- Autism Spectrum Disorder A total of 2 participants were screened and enrolled, with no screening failure. Both enrolled participants have completed study discontinuation.
Study recruitment is currently ongoing.
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
- •Treatment refractory obsessive-compulsive disorder:
- •Aged 18~65 when signing informed consent, outpatient or inpatient, male or female.
- •Fits DSM-5 obsessive-compulsive disorder criteria.
- •Fits treatment refractory obsessive-compulsive disorder criteria (both i and ii):
- •i.Treated with at least 3 kinds of serotonin reuptake inhibitors (SSRIs) with at least 2 kinds of 2nd generation antipsychotic medication as enhancement, enough dosage and enough course of treatment, and still no effect or intolerant.
- •ii.While using enough dosage of SSRIs, treated with more than 8~12 times of Cognitive Behavior Therapy (CBT) or CBT-intolerant.
- •d)Y-BOCS score ≥ 25 in screening period and baseline. e)CGI-S score ≥ 4 in screening period and baseline. f)Patient and guardian agree to DBS implant and sign informed consent after fully understood research aims, contents, anticipated treatments and risks.
- •Treatment refractory schizophrenia:
- •Aged 18~65 when signing informed consent, outpatient or inpatient, male or female.
- •Fits DSM-5 schizophrenia criteria.
- •Course of disorder ≥ 5 years.
- •Fits treatment refractory schizophrenia criteria, one of the conditions below:
- •i.Treated with more than 2 different anti-psychotic medications (clozapine excluded), enough dosage (equivalent dosage as chlorpromazine ≥ 600mg/day), enough course of treatment (≥ 12 weeks), no effect or intolerant.
- •ii.Treated with enough dosage of clozapine (≥ 300mg/day or blood medication concentration ≥ 350ng/ml, enough course of treatment (≥ 12 weeks), no effect or intolerant.
- •e)PANSS score ≥ 70 in screening period and baseline, and at least 1 item from 5 items (P1, P2, P3, P5, P6) of PANSS positive symptom scale ≥ 4; or at least 3 items from PANSS negative symptom scale (N1~N7) ≥ 4, or at least 2 items ≥
- •f)CGI-S ≥ 4 in screening period and baseline. g)GAF ≤ 60 in screening period and baseline. h)Patient and guardian agree to DBS implant and sign informed consent after fully understood research aims, contents, anticipated treatments and risks.
- •Treatment refractory bipolar with depression:
- •Aged 18~65 when signing informed consent, outpatient or inpatient, male or female.
- •Fits DSM-5 bipolar I or bipolar II criteria, currently with depression episode.
- •Course of disorder ≥ 2 years.
- •Fits treatment refractory bipolar with depression criteria (treated with two different kinds of treatment below, enough dosage and enough course of treatment ≥ 8 weeks, and cannot acquire symptom cure for 8 consecutive weeks, either i or ii):
- •i.Used at least two medications (alone) among Olanzapine (10-20mg/d) + Fluoxetine (20-60mg/d), Quetiapine (200-600mg/d), Lurasidone (40-160mg/d), Lamotrigine (200-400mg/d) ii.Used at least one medication above (alone), and used one of medication above with another medication among Lamotrigine (200-400mg/d), Valproate (1000-2000mg/d) and lithium salt (blood lithium reaches 0.8mmol/L).
- •e)Upon medication treatment, electroconvulsive therapy ≥ 12 times, no effect or failed (such as intolerant).
- •f)Fits severe symptom criteria: i.Depression episode ≥ 12 weeks in screening period. ii.MADRS score ≥ 26 in screening period and baseline. iii.GCI-BP score ≥ 4 in screening period and baseline. iv.YMRS score ≥ 12 in screening period and baseline. g)Patient and guardian agree to DBS implant and sign informed consent after fully understood research aims, contents, anticipated treatments and risks.
- •Treatment refractory anorexia nervosa:
- •Aged 18~65 when signing informed consent, outpatient or inpatient, male or female.
- •Fits DSM-5 anorexia nervosa criteria, consider both restricting type and binge-eating/purging type.
- •10 ≤ BMI < 16 in screening period and baseline.
- •Fits treatment refractory anorexia nervosa criteria (both i, ii, iii and iv):
- •i.Course of disorder ≥ 5 years, severe and sustained anorexia nervosa. ii.With ≥ 3 times repeated inpatient history and bad treatment effect (can't complete treatment or immediate relapse after treatment).
- •iii.Through systemic nutrient treatment, medication (SSRIs and/or anti-psychotics), psychotherapies (such as reinforced CBT, FBT treatment), no effect or intolerant.
- •iv.Worsened instability of clinical treatment, refuse treatment or bad reaction to reinforced treatment, last for more than 1 year, with more than 2 times of involuntary food intake.
- •e)Patient and guardian agree to DBS implant and sign informed consent after fully understood research aims, contents, anticipated treatments and risks.
- •Gambling disorder:
- •Aged 18~65 when signing informed consent, outpatient or inpatient, male or female.
- •Course of disorder ≥ 2 years.
- •Diagnosed as gambling disorder based on DSM-5, fits medium or severe diagnostic standard (≥ 6 terms)
- •Received systemic treatment (such as medication and social mental intervention) but still has iterative thoughts of impulse or gambling behaviors.
- •Patient and guardian agree to DBS implant and sign informed consent after fully understood research aims, contents, anticipated treatments and risks.
- •Adult autism:
- •Aged 18~65 when signing informed consent, outpatient or inpatient, male or female.
- •Fits DSM-5 autism spectrum disorder diagnostic standard, and there's severe, life-threatening iterative behaviors, and independently evaluated by two psychiatric doctors.
- •AuBC score ≥ 62 in screening period and baseline.
- •CGI-S score ≥ 4 in screening period and baseline.
- •Course of disorder ≥ 10 years, received systemic behavior intervention or training ( such as critical reaction training, cognitive behavior intervention, language expression training, demonstration method, natural environment training, patriarch training, social skill training, intervention based on story tales, etc. ) but failed, or intolerant.
- •Patient and guardian agree to DBS implant and sign informed consent after fully understood research aims, contents, anticipated treatments and risks.
排除标准
- •With mental disorders including physical mental disorders, paranoid personality disorder, delayed mental development etc.
- •Through clinical evaluation by investigators, there exists significant suicide behavior risk.
- •From screening period to baseline, patients who has significant improvement in evaluation scores:
- •Obsessive compulsive disorder: Y-BOCS score decreased (or improved) ≥ 20%
- •Schizophrenia: PANSS score decreased (or improved) ≥ 20%
- •Bipolar with depression: MADRS score decreased (or improved) ≥ 20%
- •Anorexia nervosa: BMI improved ≥ 20%
- •Gambling: through evaluation by investigators, online gambling behavior is significantly improved
- •Adult autism: AuBC score decreased (or improved) ≥ 20%.
- •With severe or unstable cardiovascular, inspiratory, liver, kidney, blood, endocrine, neural system or other system disorders.
- •Has neural system disorders including physical brain disorders, brain trauma, treatment-refractory seizure etc.
- •During screening period or baseline, abnormalities in patient's physical examination, laboratory examination, electrocardiogram examination, imaging examination have significant clinical meaning, and patients who are considered unfit by investigators.
- •Implanted artificial cochlea, pacemaker, similar single-side or double-side products or experienced other physical surgeries within half a year that are considered to have effect on this trial by investigators.
- •DBS implant surgery taboos present and is considered unfit by investigators.
- •Diagnosed as HIV positive.
- •Female in gestation, lactation, or blood HCG / urine gestation test positive. Or patients who can't take effective contraception actions during the trial. Or patients planning to birth or give birth after the trial begins for 3 months.
- •Currently involved or involved in other medication or medical device clinical trials 3 months before the screening period.
- •Other patients who are considered unfit by investigators.
研究组 & 干预措施
DBS intervention group
This is a single arm, prospective, open label clinical study, participants who fit inclusion standards, don't fit exclusion standards and fit surgical implantation standard will start DBS system stimulation and adjust parameters after 7-14 days of implantation. Then after stimulation for 8-24 weeks, they will be evaluated for treatment efficacies. This study is extendable, with agreements from participants, long term efficacy and safety follow-up study will be performed after 24 weeks ± 7 days, specific plan depends on different mental disorders.
干预措施: deep brain stimulation (Device)
结局指标
主要结局
reduce rate of PANSS score compared to baseline after 12 weeks of stimulation
时间窗: 12 weeks
reduce rate of Positive and Negative Syndrome Scale (PANSS) score compared to baseline after 12 weeks of stimulation. The PANSS is a medical scale used for measuring symptom severity of patients with schizophrenia. Composed of three scles: The positive scale has 7 items (minimum score 7, maximum score 49), negative scale has 7 items (minimum score 7, maximum score 49), general psychopathology scale has 16 items (minimum score 16, maximum score 112). Together, PANSS total score minimum 30 (no symptom), maximum 210 (extreme).
the duration of abstinence in gambling disorder
时间窗: within 24 weeks
within 24 weeks of stimulation, longest consecutive days without gambling
change of AuBC score compared to baseline after 12 weeks of stimulation
时间窗: 12 weeks
change of Autism Behavior Checklist (AuBC) score compared to baseline after 12 weeks of stimulation. The Autism Behavior Checklist (AuBC) is a 57-item behavior rating scale assessing the behaviors and symptoms of autism for children 3 and older. Total score 228, minimum score 57, maximum score 228.
change of Y-BOCS score compared to baseline after 12 weeks of stimulation
时间窗: 12 weeks.
change of Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score compared to baseline after 12 weeks of stimulation. The Y-BOCS is a test to rate the severity of obsessive-compulsive disorder (OCD) symptoms. Total of 10 items, total score is 40, minimum score is 0 (no symptom) , maximum score is 40 (extreme).
change of Montgomery-Åsberg Depression Rating Scale (MADRS) score compared to baseline after 12 weeks of stimulation
时间窗: 12 weeks
change of Montgomery-Åsberg Depression Rating Scale (MADRS) score compared to baseline after 12 weeks of stimulation. The MADRS is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Total score is 54, minimum score 0 (normal/symptom absent), maximum score 54 (severe).
change of BMI compared to baseline after 12 weeks of stimulation
时间窗: 12 weeks
change of BMI compared to baseline after 12 weeks of stimulation. Weight and height will be combined to report BMI in kg/m\^2.
次要结局
- Treatment efficacy rate in OCD(within 24 weeks)
- Change in Y-BOCS score compared to baseline after 8/24 weeks of stimulation. Change of Y-BOCS score in OCD(within 24 weeks)
- Change of CGI-S score in OCD(within 24 weeks)
- Change of HAMD-17 score in OCD(within 24 weeks)
- CGI-I score in OCD(within 24 weeks)
- Sheehan Disability Scale score in OCD(within 24 weeks)
- Reduce rate of PANSS score in schizophrenia(within 24 weeks)
- Reduce rate of PANSS positive symptoms(within 24 weeks)
- Reduce rate of PANSS negative symptoms(within 24 weeks)
- Change of HAMA score in OCD(within 24 weeks)
- Treatment efficacy rate in schizophrenia(within 24 weeks)
- Change in Global Assessment of Function (GAF) score in schizophrenia(within 24 weeks)
- Change of CGI-S score in schizophrenia(within 24 weeks)
- CGI-I score in schizophrenia(within 24 weeks)
- Change of MADRS score in bipolar with depression(within 24 weeks)
- Treatment efficacy rate in bipolar with depression(within 24 weeks)
- Change of YMRS score in bipolar with depression(within 24 weeks)
- Change of Pittsburgh Sleep Quality Index (PSQI) in bipolar with depression(within 24 weeks)
- Change of Barratt Impulsivity Scale-11 in anorexia nervosa(within 24 weeks)
- Symptom relieve rate in bipolar with depression(within 24 weeks)
- Change of HAMD-17 score in bipolar with depression(within 24 weeks)
- Change of CGI-BP-S score in bipolar with depression(within 24 weeks)
- CGI-I score in bipolar with depression(within 24 weeks)
- Change of SDS in bipolar with depression(within 24 weeks)
- Change of BMI in anorexia nervosa(within 24 weeks)
- Change of Eating Disorder Examination Questionnaire 6.0 in anorexia nervosa(within 24 weeks)
- Change of CGI-S score in anorexia nervosa(within 24 weeks)
- Change of HAMD-17 score in anorexia nervosa(within 24 weeks)
- Change of HAMA score in anorexia nervosa(within 24 weeks)
- Change of Y-BOCS score in anorexia nervosa(within 24 weeks)
- CGI-I score in anorexia nervosa(within 24 weeks)
- duration of abstinence in gambling disorder(within 24 weeks)
- Subjective craving in gambling disorder(within 24 weeks)
- Change of GCI-S score in autism disorder(within 24 weeks)
- Change of Aberrant Behavior Checklist (AbBC) scorein autism disorder(within 24 weeks)
- CGI-I score in autism disorder(within 24 weeks)
- Change of HAMD-17 in gambling disorder(within 24 weeks)
- Change of HAMA in gambling disorder(within 24 weeks)
- Change of SDS in gambling disorder(within 24 weeks)
- Change of AuBC score in autism disorder(within 12 weeks)
- Change of ADL score in autism disorder(within 24 weeks)
研究者
Zhen Wang
Principal investigator
Shanghai Mental Health Center