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Comparison of Efficacy and Safety Between Sodium Valproate and ECT Adjunction in Clozapine-treated Refractory Schizophrenia

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ClinicalTrials.gov Identifier: NCT03652974
Recruitment Status : Enrolling by invitation
First Posted : August 31, 2018
Last Update Posted : August 31, 2018
Sponsor:
Information provided by (Responsible Party):
Shanghai Mental Health Center

Brief Summary:
In this study, investigators designed a double-blind randomized trial to compare the efficacy and safety between sodium valproate and electroconvulsive therapy (ECT) adjunction in clozapine-treated refractory schizophrenia.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: sodium valproate with Clozapine Device: modified electroconvulsive therapy(MECT) with Clozapine Not Applicable

Detailed Description:

Schizophrenia is one of the most serious mental illnesses worldwide that affects approximately 1% of the worldwide population and result in a heavy economic burden to affected family. Antipsychotics are the main stay of treatment of schizophrenia, however, there are still approximately 1/3 schizophrenia patients who does not responded to the antipsychotic agents, and these patients easily develop into treatment-refractory schizophrenia (TRS).

Clozapine is the only evidence based effective medication for treatment-refractory schizophrenia (TRS). In spite of its prominent efficacy, approximately 1/3-2/1 treatment-refractory schizophrenia (TRS) treated with clozapine still present with significant residual psychotic symptoms and negative symptoms. As such, over time, clinicians struggled to find strategies to improve outcome by augmenting the concomitant psychiatric treatments, including not only combining antipsychotics but also combining a mood stabilizer or electroconvulsive therapy (ECT).

Both electroconvulsive therapy (ECT) and antiepileptic drugs, such as sodium valproate, shares anticonvulsant properties and anticonvulsant effect relate to clinical efficacy. In 1983, Sackeim et al. pointed out that electroconvulsive therapy (ECT)-induced cortical gamma-aminobutyric-acid (GABA) depletion may be the reason for its anticonvulsant action. In addition, the effect of electroconvulsive therapy (ECT) on the gamma-aminobutyric-acid (GABA) system was confirmed by several studies. Interestingly, it has been reported that the therapeutic effect of sodium valproate combined with antipsychotics is closely related to gamma-aminobutyric-acid (GABA) system. The study of the efficacy of sodium valproate or electroconvulsive therapy (ECT) combined with antipsychotics on schizophrenia may have interesting findings.

The primary objective of this study was to compare the efficacy and safety between sodium valproate and electroconvulsive therapy (ECT) adjunction in clozapine-treated refractory schizophrenia during a 8 weeks period.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Drug: sodium valproate with Clozapine sodium valproate 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: Magnetic seizure therapy(MST) with Clozapine
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Comparison of Efficacy and Safety Between Sodium Valproate and ECT Adjunction in Clozapine-treated Refractory Schizophrenia
Actual Study Start Date : August 1, 2018
Estimated Primary Completion Date : February 1, 2019
Estimated Study Completion Date : August 1, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arm Intervention/treatment
Experimental: sodium valproate with clozapine

sodium valproate, dosage form: 250 mg, dosage and frequency:250 mg/d for 1 week, 500 mg/d for weeks 2 and 3, 1000 mg/d for weeks 5, 6, 7 and 8; clozapine, dosage and frequency:300~600 mg/d; duration: 8th week.

Intervention: Drug: sodium valproate with Clozapine

Drug: sodium valproate with Clozapine
sodium valproate may be used as a synergistic agent of clozapine in the treatment of treatment-refractory schizophrenia
Other Name: Valproate

Experimental: Modified electroconvulsive therapy with clozapine

12 times MECT for 8 weeks,2 times a week for the first four weeks, and then turn to once a week for the next four weeks; clozapine, dosage and frequency:300~600 mg/d; duration: 8th week.

Intervention: Device: modified electroconvulsive therapy(MECT) with Clozapine

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-refractory schizophrenia




Primary Outcome Measures :
  1. Positive and Negative Syndrome Scale (PANSS) used to assess the effectiveness of treatment [ Time Frame: the baseline ]
    The battery of Positive and Negative Syndrome Scale (PANSS) test will be administered in a 30-minute sessions to assess the effectiveness of treatment

  2. Positive and Negative Syndrome Scale (PANSS) used to assess the effectiveness of treatment [ Time Frame: the end of fourth week ]
    The battery of Positive and Negative Syndrome Scale (PANSS) test will be administered in a 30-minute sessions to assess the effectiveness of treatment

  3. Positive and Negative Syndrome Scale (PANSS) used to assess the effectiveness of treatment [ Time Frame: the end of the eighth week ]
    The battery of Positive and Negative Syndrome Scale (PANSS) test will be administered in a 30-minute sessions to assess the effectiveness of treatment



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The diagnosis of schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
  • 18~60 years old
  • Clozapine resistance was defined as a history of persistence of psychotic symptoms after a trial of clozapine of at least 12 weeks, at a blood level ≥350 ng/mL
  • Signed an informed consent

Exclusion Criteria:

  • Patients to be diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) for substance abused, development delayed
  • Suffering from serious physical disease and can not accept the treatment
  • Allergic to sodium valproate, 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03652974


Locations
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China, Shanghai
Shanghai Mental Health Center
Shanghai, Shanghai, China, 200030
Sponsors and Collaborators
Shanghai Mental Health Center

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Responsible Party: Shanghai Mental Health Center
ClinicalTrials.gov Identifier: NCT03652974     History of Changes
Other Study ID Numbers: 81171272
First Posted: August 31, 2018    Key Record Dates
Last Update Posted: August 31, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Shanghai Mental Health Center:
Schizophrenia, clozapine, valproate, ECT
Additional relevant MeSH terms:
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Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Valproic Acid
Clozapine
Anticonvulsants
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin Antagonists
Serotonin Agents
Antipsychotic Agents
GABA Antagonists