Efficacy and Safety of Combo-stim Deep Brain Stimulation... | NCT06112067

Name	Class
SceneRay Corporation, Limited	INDUSTRY
Huashan Hospital	OTHER
Shanghai 6th People's Hospital	OTHER
Changhai Hospital

Label	Type	Description	Intervention Names
DBS intervention group	Experimental	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.	Device: deep brain stimulation

Name	Type	Description	Arm Group Labels	Other Names
deep brain stimulation	Device	DBS electrodes will be implanted into the ALIC and the NAcc, electric stimulation of those areas are used to treat mental disorders and to evaluate the efficacy and safety of DBS system.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
change of Y-BOCS score compared to baseline after 12 weeks of stimulation	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).	12 weeks.
reduce rate of PANSS score compared to baseline after 12 weeks of stimulation	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).	12 weeks
change of Montgomery-Åsberg Depression Rating Scale (MADRS) score compared to baseline after 12 weeks of stimulation	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).	12 weeks
change of BMI compared to baseline after 12 weeks of stimulation	change of BMI compared to baseline after 12 weeks of stimulation. Weight and height will be combined to report BMI in kg/m^2.	12 weeks
the duration of abstinence in gambling disorder

Secondary Outcomes

Measure	Description	Time Frame
Treatment efficacy rate in OCD	the number of treatment-response patient/total patient*100% after 8/12/24 weeks of stimulation. The Y-BOCS score reduce rate ≥ 35% and Clinical Global Impression Scale (CGI-I) score being 1 or 2 means treatment response.	within 24 weeks
Change in Y-BOCS score compared to baseline after 8/24 weeks of stimulation. Change of Y-BOCS score in OCD

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Treatment refractory obsessive-compulsive disorder:
1. Aged 18~65 when signing informed consent, outpatient or inpatient, male or female.
2. Fits DSM-5 obsessive-compulsive disorder criteria.
3. 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:
1. Aged 18~65 when signing informed consent, outpatient or inpatient, male or female.
2. Fits DSM-5 schizophrenia criteria.
3. Course of disorder ≥ 5 years.
4. 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 ≥ 5.

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:
1. Aged 18~65 when signing informed consent, outpatient or inpatient, male or female.
2. Fits DSM-5 bipolar I or bipolar II criteria, currently with depression episode.
3. Course of disorder ≥ 2 years.
4. 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:
1. Aged 18~65 when signing informed consent, outpatient or inpatient, male or female.
2. Fits DSM-5 anorexia nervosa criteria, consider both restricting type and binge-eating/purging type.
3. 10 ≤ BMI < 16 in screening period and baseline.
4. 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:
1. Aged 18~65 when signing informed consent, outpatient or inpatient, male or female.
2. Course of disorder ≥ 2 years.
3. Diagnosed as gambling disorder based on DSM-5, fits medium or severe diagnostic standard (≥ 6 terms)
4. Received systemic treatment (such as medication and social mental intervention) but still has iterative thoughts of impulse or gambling behaviors.
5. Patient and guardian agree to DBS implant and sign informed consent after fully understood research aims, contents, anticipated treatments and risks.
Adult autism:
1. Aged 18~65 when signing informed consent, outpatient or inpatient, male or female.
2. Fits DSM-5 autism spectrum disorder diagnostic standard, and there's severe, life-threatening iterative behaviors, and independently evaluated by two psychiatric doctors.
3. AuBC score ≥ 62 in screening period and baseline.
4. CGI-S score ≥ 4 in screening period and baseline.
5. 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.
6. Patient and guardian agree to DBS implant and sign informed consent after fully understood research aims, contents, anticipated treatments and risks.

Exclusion Criteria:

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:
1. Obsessive compulsive disorder: Y-BOCS score decreased (or improved) ≥ 20%
2. Schizophrenia: PANSS score decreased (or improved) ≥ 20%
3. Bipolar with depression: MADRS score decreased (or improved) ≥ 20%
4. Anorexia nervosa: BMI improved ≥ 20%
5. Gambling: through evaluation by investigators, online gambling behavior is significantly improved
6. 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.

ID	Term
D009771	Obsessive-Compulsive Disorder
D012559	Schizophrenia
D000856	Anorexia Nervosa
D005715	Gambling
D001321	Autistic Disorder

ID	Term
D001008	Anxiety Disorders
D001523	Mental Disorders
D019967	Schizophrenia Spectrum and Other Psychotic Disorders
D001068	Feeding and Eating Disorders

ID	Term
D004599	Electric Stimulation Therapy
D013812	Therapeutics
D013514	Surgical Procedures, Operative