SMART Design to Compare Antipsychotic Treatments in Treatment-Resistant Schizophrenia

Phase 3

• Conditions: Treatment-resistant Schizophrenia
• Interventions: Device: MECT; Device: DBS; Drug: Clozapine

• Registration Number: NCT04528095
• Lead Sponsor: Shanghai Mental Health Center

Brief Summary

The project intends to take treatment-resistant schizophrenia as the research object and uses sequential multiple assignment randomized trial(SMART) design to define the treatment recommendations of different drug regimen for treatment resistant schizophrenia and to determine the physical enhancement regimen for clozapine-resistant schizophrenia and to explore targeted regulation scheme for ultra-resistant schizophrenia.

Detailed Description

This trial is a sequential multiple-assignment RCT design of antipsychotic drugs, planning to recruit 162 people with treatment-resistant schizophrenia followed for 12 months. The study includes three treatment phases and a naturalistic follow-up phase. Participants who meet the response criteria remain on that treatment for the duration of 12-month treatment. If the participants fail the treatment or can't tolerant the side effects, the patient moves to the next phase of the study to receive a new treatment.

Study Timeline

• Status Verified: 2020-08
• Study First Submitted: 2020-08-12
• Study First Submitted QC: 2020-08-22
• Last Update Submitted: 2020-08-22
• Study First Posted: 2020-08-27
• Last Update Posted: 2020-08-27
• Study Start: 2020-12
• Primary Completion: 2022-12
• Study Completion: 2022-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 162

Inclusion Criteria

1. meet the DSM-5 diagnostic criteria for schizophrenia,
2. be 18-55 years of age,
3. treatment-resistant schizophrenia:no response to sufficient doses (400-600 mg/ day CPZ equivalent) of at least two antipsychotics in the past 5 years,
4. Informed consent.

Exclusion Criteria

1. Patients with medical or psychiatric comorbidities and those who require concomitant other medications are excluded.
2. Patients with contraindications to even one of the proposed treatment arms are excluded.
3. Patients with risks such as extreme agitation, stupor or suicide are excluded.
4. Female patients with pregnancy or breast-feeding are also excluded.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
MST	MECT	MST:The treatment lasted for 4 months,16 times in total
MECT	MECT	MECT:The treatment lasted for 4 months,16 times in total
DBS	DBS	Two electrode emplacement groups (target nucleus accumbens and hippocampus respectively)
Clozapine	Clozapine	Clozapine 400 \~ 600mg/d or plasma concentration \>350ng/ml
Clozapine+Amisulpride	Clozapine	Clozapine 400 \~ 600mg/d or plasma concentration \>350ng/ml Amisulpride 200-800mg/d
Clozapine+Gingke biloba	Clozapine	Clozapine 400 \~ 600mg/d or plasma concentration \>350ng/ml Gingke biloba 120-360mg/d

Primary Outcome Measures

Name	Time	Method
Response rate	Change from baseline PANSS score at 12 weeks	25% or greater change in Positive and Negative Syndrome Scale (PANSS)

Secondary Outcome Measures

Name	Time	Method
Adverse reactions	baseline, 4 weeks, 8 weeks, 12 weeks, 14 weeks, 16 weeks,32 weeks	Abnormal Involuntary Movement Scale (AIMS) (0,42,higher scores mean a worse outcome)
Neurocognitive assessments and social function	baseline, 6 weeks, 3 months, 6 months, 9 months, 12 months	The MATRICS consensus cognitive battery (MCCB) has been widely used to evaluate cognitive deficits in schizophrenia patients(0%,100%,higher scores mean a better outcome)
Clinical assessements	baseline, 4 weeks, 8 weeks, 12 weeks, 14 weeks, 16 weeks,32 weeks	Clinical Global Impression Scale-Severity (CGI-S) (0,7,higher scores mean a worse outcome)

Trial Locations

Locations (1)

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China