Clinical trial NCT06456983: Maintenance ElectroConvulsive Therapy in Clozapine RESISTant Schizophrenia - the MECT-RESIST Trial
Official title: Maintenance ElectroConvulsive Therapy in Clozapine RESISTant Schizophrenia - the MECT-RESIST Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Schizophrenia
Treatment Resistant Schizophrenia
Keywords: electroconvulsive therapy
ECT
Lead sponsor: Central Institute of Mental Health, Mannheim
Sponsor class: OTHER
First posted: 2024-06-13
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a multi-center, observer-blind, randomized, and actively controlled parallel-group clinical trial to examine the effectiveness of mECT in clozapine resistant patients with schizophrenia (CRS) who improved after a full course of routine ECT.
Primary purpose: TREATMENT

Brief summary: Schizophrenia is one of the most severe and costliest mental disorders in terms of human suffering and societal expenditure. About 15-30% of patients do not respond to all known antipsychotics, including clozapine, the current gold-standard in these cases. Hence, a recent Cochrane review stated that the quality of the existing studies is too poor to recommend any intervention in addition to clozapine and that new, randomized controlled trials independent from the pharmaceutical industry need to be performed to substantially improve patient care. Although electroconvulsive therapy (ECT) was initially used to treat schizophrenia, it is nowadays by far underused in the therapy of schizophrenia in many countries. ECT is well known to be highly effective in clozapine-treatment-resistant schizophrenia (CRS), and synergistic effects of clozapine and ECT have been demonstrated. However, relapse rates after successful courses of ECT are still very high, and evidence for maintenance ECT (mECT) in CRS is scarce at best. In a multi-center trial the investigators aim to examine the effectiveness of mECT in treatment-resistant patients with schizophrenia who improved after a course of routine ECT. If mECT will lead to a later timepoint of relapse and/or to a higher proportion of relapse-free patients compared to those undergoing treatment as usual, this trial would have an enormous impact on therapeutic strategies for "treatment-resistant" patients and would induce a profound change of current treatment guidelines, where ECT still ranks at the level of ultima ratio, despite accumulating evidence suggesting otherwise.

Detailed description: The scientific aim of the study is to conduct a multicenter, blinded, randomized and actively controlled trial to test the hypothesis that maintenance ECT (mECT) plus clozapine is superior to treatment with clozapine alone in CRS. Prior to the start of mECT (phase II), an acute ECT series (phase I) should have already led to a significant clinical improvement in CRS patients. The superiority of mECT will be proven by a longer time to relapse and secondarily by a lower number of patients with relapse compared to the control group.

Secondary objectives are to test the hypotheses that the global level of functioning and quality of life will increase, and that depression, overall symptoms of the schizophrenic syndrome, concomitant catatonic symptoms, stress and self-stigmatization will decrease compared to the control group. It is also expected that cognitive performance will not only not deteriorate, but will improve over the course of the mECT.

Once the positive ethics votes have been obtained, the first patients will be included at the individual centers following successful center initiation. In month 12 at the latest, the first patient should leave phase I after 6 weeks as a responder and will be randomized in phase II (clozapine versus clozapine plus mECT). At month 30 the last patient (total n = 84) should have been randomized as a responder from phase I and been included in phase II. At month 36 the last planned patient completes phase II of the study with his/her last study visit. Accordingly, he/she is the last patient to start the 12-month follow-up phase. In month 46 investigators will start final data evaluation and analysis. Investigators will complete the primary publication of the study this time point. After 4 years the last patient completes the 12-month follow-up phase. At study end final data evaluation and analysis regarding the primary endpoint of the follow-up phase takes place as well as the completion and submission of the primary publication of the follow-up.

Eligibility criteria: Inclusion Criteria:

* Current schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), BPRS total score \> 45 and history of clozapine resistant schizophrenia (CRS), which will include treatment-resistant schizophrenia with clozapine intolerance or absolute contraindications for clozapine;

Exclusion Criteria:

1. Diagnosis of DSM-5 major neurocognitive disorder ("dementia"), current severe substance-use disorder, affective disorders with psychotic symptoms or any personality disorder;
2. Inability to read/write German or inability to provide written informed consent;
3. Pregnancy or breast-feeding;
4. General medical condition contraindicating ECT.

Primary outcomes:
measure: Time to relapse
timeFrame: 28 weeks (duration of PHASE 2)
Secondary outcomes:
measure: Number of relapse free subjects
timeFrame: after 28 weeks, i.e. end of Phase 2
measure: BPRS
timeFrame: after 28 weeks, i.e. end of Phase 2
measure: GAF:
timeFrame: after 28 weeks, i.e. end of Phase 2
measure: SLSSWB:
timeFrame: after 28 weeks, i.e. end of Phase 2
measure: PANSS:
timeFrame: after 28 weeks, i.e. end of Phase 2
measure: HAMD:
timeFrame: after 28 weeks, i.e. end of Phase 2
measure: NCRS-dv:
timeFrame: after 28 weeks, i.e. end of Phase 2
measure: Q-LES-Q-18:
timeFrame: after 28 weeks, i.e. end of Phase 2
Other outcomes:
measure: Cognition: MMSE:
timeFrame: after 28 weeks, i.e. end of Phase 2
measure: THINC-it:
timeFrame: after 28 weeks, i.e. end of Phase 2
Locations:
city: Aachen
country: Germany
facility: Dept. of Psychiatry, RWTU Aachen
city: Augsburg
country: Germany
facility: Dept. of Psychiatry, University of Augsburg
city: Göppingen
country: Germany
facility: Klinik für Psychiatrie, Göppingen
city: Göttingen
country: Germany
facility: Departmet of Psychiatry, University Medical Center Göttingen
city: Hannover
country: Germany
facility: Dept. of Psychiatry, Hannover Medical School
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg, Klinik für Allgemeine Psychiatrie
city: Ingolstadt
country: Germany
facility: Zentrum für Psychische Gesundheit
city: Mainz
country: Germany
facility: Dept. of Psychiatry, University Mainz
city: Mannheim
country: Germany
facility: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health (CIMH)
city: München
country: Germany
facility: Dept. of Psychiatry, LMU München
city: Saarbrücken
country: Germany
facility: Clinic for Psychiatry, Saarbrücken
city: Siegen
country: Germany
facility: Klinik für Psychiatrie, Siegen
city: Tübingen
country: Germany
facility: Dept. of Psychiatry, University Tübingen
city: Wiesloch
country: Germany
facility: Dept. of Psychiatry I, Wiesloch
Study officials:
affiliation: Central Institute of Mental Health (CIMH), Mannheim, Germany
name: Alexander Sartorius, Prof
role: PRINCIPAL_INVESTIGATOR
References: