Comparison of Maintenance ECT Versus Clozapine in Treatment-resistant Schizophrenia

Study Overview
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Brief Summary
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The proposed study will be conducted to compare the efficacy of maintenance ECT (M-ECT) vs Clozapine in treatment resistant schizophrenia (TRS) in terms of change in psychopathology measures and cerebral hemodynamics.

Detailed Description
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The proposed study is a prospective, randomized clinical trial in patients suffering from treatment-resistant schizophrenia (TRS) and will be conducted in the Department of Psychiatry, AIIMS, Bhubaneswar, over a period of 16 months. Sixty patients with TRS (TRRIP consensus criteria, 2017), fulfilling the inclusion and exclusion criteria will be recruited for the study. Written informed consent will be taken after explaining the objectives and procedure of the study in detail. The detailed history, relevant social-demographic and clinical data will be collected in a structured case record form (CRF). At baseline, PANSS will be administered to determine the severity of positive symptoms, negative symptoms, and general psychopathology, Global assessment of functioning (GAF), and CGI to determine the baseline severity of the illness and improvement with treatment and MoCA to assess change in cognitive impairment. Before starting the treatment, brain SPECT-CT will be done to measure baseline regional brain blood perfusion. The study cohort will be randomized into two treatment groups by computer-generated random numbers, each group comprising 30 patients. One group will receive maintenance ECT (M-ECT) following acute treatment of bilateral ECT of six sessions along with ongoing antipsychotic and the other group will be treated with Clozapine monotherapy. PANSS, GAF, CGI, MoCA will be re-administered at 6 weeks, 3 months, and 6 months follow-up visits to compare the changes within each group and between the groups. Post-treatment SPECT-CT of the brain will be done at the end of 6 months to document changes in the regional cerebral blood perfusion.

Official Title
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Comparison of Maintenance ECT Versus Clozapine on Psychopathology and Cerebral Hemodynamics in Treatment-resistant Schizophrenia: A Randomized Controlled Trial

Conditions
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Treatment Resistant Schizophrenia

Intervention / Treatment
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* Other: Bilateral M-ECT
* Drug: Clozapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients clinically diagnosed with treatment-resistant schizophrenia (TRS) (TRRIP consensus criteria). Patients aged 18-60 years of either sex. Patients giving voluntary written consent for participation in the study Exclusion Criteria: Patient already on Clozapine or ECT. History of psychoactive substance abuse or dependence. Co-morbid psychiatric, major medical, or neurological disorders. History of organicity or significant head injury. Pacemaker or metal in any part of the body excluding the mouth. Pregnant and breastfeeding females.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test group<br>Bilateral Maintenance ECT (B/L M-ECT) | Other: Bilateral M-ECT<br>* Following acute treatment with bilateral ECT of 6 sessions over a period of two weeks, Bilateral M-ECT will be administered at a frequency of 1 session/week for one month, then 1 session / 2 weeks for 2 months and then 1 session/month for next 3 months.<br>|
| Active Comparator: Control group<br>Clozapine monotherapy. Clozapine will be given in accordance with Maudsley guideline: 12.5 mg on the first day, followed by 12.5mg twice daily on the second day, followed by 25mg twice daily for next two days and then increment of 25mg every two days till the target dose of 250-400 mg per day in two divided doses as per tolerability of the patients | Drug: Clozapine<br>* Clozapine will be given in accordance with Maudsley guideline: 12.5 mg on the first day, followed by 12.5mg twice daily on the second day, followed by 25mg twice daily for next two days and then increment of 25mg every two days till the target dose of 250-400 mg per day in two divided doses as per tolerability of the patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in severity of psychopathology | Severity will be assessed by Positive and Negative Symptom Scale (PANSS) PANSS Score ranges from 30- 210. A higher score represents more severe psychopathology | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in illness severity, and global improvement with treatment | Assessed by change in Clinical Global Impression Schizophrenia (CGI-SCH) scores. | 24 weeks | 
| Change in global functionality | Assessed by change in Global assessment of functioning (GAF) scores. | 24 weeks | 
| Change in Cognitive impairment | Assessed by change in Montreal Cognitive Assessment (MoCA) scores. | 24 weeks | 
| Number of patients receiving rescue medications. | Patients with treatment relapse or treatment non-response will receive rescue medications. | 24 weeks | 
| Change in regional cerebral blood flow | Change in regional cerebral blood flow will be measured by SPECT-CT Brain | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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M-ECT, Clozapine, Psychopathology, Cerebral perfusion