Disturbance of Plasma Cytokine Parameters in Clozapine-Resistant Treatment-Refractory Schizophrenia (CTRS) and Their Association With Combination Therapy

NCT03652974 | Completed Phase 4 DMC

• 1 other identifier: 81171272
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, investigators designed a double-blind randomized trial to compare the efficacy and safety between sodium valproate, amisulpride and MECT combination therapy in clozapine-treated refractory schizophrenia (CTRS).

Conditions

Schizophrenia

Keywords

Schizophrenia， clozapine， amisulpride, valproate， ECT, cytokine

Outcome Measures

Primary Outcomes (17)

• Positive and Negative Syndrome Scale (PANSS)

  The battery of Positive and Negative Syndrome Scale (PANSS) test will be administered in a 30-minute sessions to evaluate the psychiatric symptoms.

  the baseline

• Positive and Negative Syndrome Scale (PANSS)

  The battery of Positive and Negative Syndrome Scale (PANSS) test will be administered in a 30-minute sessions to evaluate the psychiatric symptoms.

  the end of the six week

• Positive and Negative Syndrome Scale (PANSS)

  The battery of Positive and Negative Syndrome Scale (PANSS) test will be administered in a 30-minute sessions to evaluate the psychiatric symptoms.

  the end of the twelve week

• Scale for the Assessment of Negative Symptoms (SANS)

  The Scale for the Assessment of Negative Symptoms (SANS) was applied to assess negative symptoms.

  the baseline

• Scale for the Assessment of Negative Symptoms (SANS)

  The Scale for the Assessment of Negative Symptoms (SANS) was applied to assess negative symptoms.

  the end of the six week

• Scale for the Assessment of Negative Symptoms (SANS)

  The Scale for the Assessment of Negative Symptoms (SANS) was applied to assess negative symptoms.

  the end of the twelve week

• Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

  The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to evaluate the cognitive performance.

  the baseline

• Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

  The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to evaluate the cognitive performance.

  the end of the six week

• Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

  The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to evaluate the cognitive performance.

  the end of the twelve week

• Clinical Global Impression (CGI)

  The Clinical Global Impression (CGI) including severity scale (CGI-S), improvement scale (CGI-I), and efficacy index (CGI-E) was used to evaluate the severity of symptoms and treatment response and treatment effect, respectively.

  the baseline

• Clinical Global Impression (CGI)

  The Clinical Global Impression (CGI) including severity scale (CGI-S), improvement scale (CGI-I), and efficacy index (CGI-E) was used to evaluate the severity of symptoms and treatment response and treatment effect, respectively.

  the end of the six week

• Clinical Global Impression (CGI)

  The Clinical Global Impression (CGI) including severity scale (CGI-S), improvement scale (CGI-I), and efficacy index (CGI-E) was used to evaluate the severity of symptoms and treatment response and treatment effect, respectively.

  the end of the twelve week

• Treatment Emergent Symptom Scale (TESS)

  The Treatment Emergent Symptom Scale (TESS) was used to assess the severity of treatment adverse events.

  the baseline

• Treatment Emergent Symptom Scale (TESS)

  The Treatment Emergent Symptom Scale (TESS) was used to assess the severity of treatment adverse events.

  the end of the six week

• Treatment Emergent Symptom Scale (TESS)

  The Treatment Emergent Symptom Scale (TESS) was used to assess the severity of treatment adverse events.

  the end of the twelve week

• plasma cytokines IL-2, IL-6 and TNF-α

  The plasma cytokines IL-2, IL-6 and TNF-α would be measured using ELISA kits (R \& D Systems, Mississauga, Ontario, CANADA).

  the baseline

• plasma cytokines IL-2, IL-6 and TNF-α

  The plasma cytokines IL-2, IL-6 and TNF-α would be measured using ELISA kits (R \& D Systems, Mississauga, Ontario, CANADA).

  the end of the twelve week

Study Arms (4)

sodium valproate with clozapine

EXPERIMENTAL

sodium valproate, dosage form: 250 mg, dosage and frequency:250 mg/d for 1 week, 500 mg/d for week 2 , 1000 mg/d for weeks 3, 4, 5, 6, 7 , 8, 9, 10, 11and 12; clozapine, dosage and frequency:300\~600 mg/d; duration: 12 weeks. Intervention: Drug: sodium valproate with Clozapine

Drug: sodium valproate with Clozapine

Modified electroconvulsive therapy with clozapine

EXPERIMENTAL

12 times MECT for 12 weeks，once a week for the 12 weeks; clozapine, dosage and frequency:300\~600 mg/d; duration: 12 weeks. Intervention: Device: modified electroconvulsive therapy(MECT) with Clozapine

Device: modified electroconvulsive therapy(MECT) with Clozapine

amisulpride

EXPERIMENTAL

amisulpride, dosage form: 200 mg, dosage and frequency:200 mg/d for 1 week, 400 mg/d for week 2,800 mg/d for weeks 3, 4, 5, 6, 7 , 8, 9, 10, 11and 12; clozapine, dosage and frequency:300\~600 mg/d; duration: 12 weeks. Intervention: Drug: amisulpride with Clozapine

Drug: amisulpride with Clozapine

placebo

PLACEBO COMPARATOR

The amisulpride and placebo tablets were identical in appearance. One placebo tablet for the first one week, two placebo tablets for the second week, four placebo tablets for weeks 3, 4, 5, 6, 7 , 8, 9, 10, 11and 12; clozapine, dosage and frequency:300\~600 mg/d; duration: 12 weeks. Intervention: Drug: placebo with Clozapine

Drug: placebo with Clozapine

Interventions

sodium valproate with Clozapine DRUG

sodium valproate may be used as a synergistic agent of clozapine in the treatment of treatment-refractory schizophrenia

Also known as: Valproate

sodium valproate with clozapine

modified electroconvulsive therapy(MECT) with Clozapine DEVICE

modified electroconvulsive therapy(MECT) may be used as a synergistic agent of clozapine in the treatment of treatment-refractory schizophrenia

Modified electroconvulsive therapy with clozapine

amisulpride with Clozapine DRUG

amisulpride may be used as a synergistic agent of clozapine in the treatment of treatment-refractory schizophrenia

amisulpride

placebo with Clozapine DRUG

placebo may be used as a synergistic agent of clozapine in the treatment of treatment-refractory schizophrenia

placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• The diagnosis of schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
• ～60 years old
• Clozapine resistance was defined as used at least two antipsychotics with different chemical structures with appropriate dosages for a sufficient duration, and recently have received stable dose of clozapine 400 mg or more per day for at least 6 months.
• Signed an informed consent

You may not qualify if:

• Patients to be diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) for substance abused, development delayed
• Suffering from serious physical disease and can not accept the treatment
• Allergic to sodium valproate, amisulpride, propofol, succinylcholine or atropine
• Participated in any clinical subject within 30 days
• Pregnancy or lactation
• Inability to sign informed consent because of capacity due due to severe mental illness, significant psychomotor agitation or slowness test completion

Sponsors & Collaborators

• Shanghai Mental Health Center: lead
• Shanghai Pudong New Area Mental Health Center: collaborator
• The Affiliated Brain Hospital of Guangzhou Medical University: collaborator

Study Sites (1)

Shanghai Mental Health Center

Shanghai, Shanghai Municipality, 200030, China

Location

Related Publications (1)

• Zhu MH, Liu ZJ, Hu QY, Yang JY, Jin Y, Zhu N, Huang Y, Shi DH, Liu MJ, Tan HY, Zhao L, Lv QY, Yi ZH, Wu FC, Li ZZ. Amisulpride augmentation therapy improves cognitive performance and psychopathology in clozapine-resistant treatment-refractory schizophrenia: a 12-week randomized, double-blind, placebo-controlled trial. Mil Med Res. 2022 Oct 18;9(1):59. doi: 10.1186/s40779-022-00420-0.

  PMID: 36253804 DERIVED

MeSH Terms

Conditions

Schizophrenia

Interventions

Valproic Acid; Clozapine; Amisulpride

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Zezhi Li, M.D.

  Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Drug: amisulpride, sodium valproate , placebo and Clozapine amisulpride, sodium valproate and placebo may be used as a synergistic agent of clozapine in the treatment of treatment-resistant schizophrenia Other Name: Valproate Device: modified electroconvulsive therapy(MECT) with Clozapine modified electroconvulsive therapy(MECT) may be used as a synergistic agent of clozapine in the treatment of treatment-resistant schizophrenia Device: Modified electroconvulsive therapy(MECT) with Clozapine

Study Record Dates

• First Submitted: August 25, 2018
• First Posted: August 31, 2018
• Study Start: September 6, 2018
• Primary Completion: August 30, 2021
• Study Completion: August 30, 2021
• Last Updated: September 6, 2022

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)