Maintenance ElectroConvulsive Therapy in Clozapine RESISTant Schizophrenia - the MECT-RESIST Trial

Schizophrenia Clinical Trial

— MECT-RESIST  

Official title:

Maintenance ElectroConvulsive Therapy in Clozapine RESISTant Schizophrenia - the MECT-RESIST Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06456983
• Other study ID #: MECT-RESIST
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 2025
• Est. completion date: July 2028

Study information

• Verified date: June 2024
• Source: Central Institute of Mental Health, Mannheim
• Contact: Alexander Sartorius, Prof
• Phone: +49-621-1703
• Email: alexander.sartorius[@]zi-mannheim.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 140
• Est. completion date: July 2028
• Est. primary completion date: July 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Schizophrenia
• Treatment Resistant Schizophrenia

Intervention

Device:
• maintenance electroconvulsive therapy (mECT)
see Arms

Locations

Country	Name	City	State
Germany	Dept. of Psychiatry, RWTU Aachen	Aachen
Germany	Dept. of Psychiatry, University of Augsburg	Augsburg
Germany	Klinik für Psychiatrie, Göppingen	Göppingen
Germany	Departmet of Psychiatry, University Medical Center Göttingen	Göttingen
Germany	Dept. of Psychiatry, Hannover Medical School	Hannover
Germany	Universitätsklinikum Heidelberg, Klinik für Allgemeine Psychiatrie	Heidelberg
Germany	Zentrum für Psychische Gesundheit	Ingolstadt
Germany	Dept. of Psychiatry, University Mainz	Mainz
Germany	Department of Psychiatry and Psychotherapy, Central Institute of Mental Health (CIMH)	Mannheim
Germany	Dept. of Psychiatry, LMU München	München
Germany	Clinic for Psychiatry, Saarbrücken	Saarbrücken
Germany	Klinik für Psychiatrie, Siegen	Siegen
Germany	Dept. of Psychiatry, University Tübingen	Tübingen
Germany	Dept. of Psychiatry I, Wiesloch	Wiesloch

Sponsors (1)

Lead Sponsor	Collaborator
Central Institute of Mental Health, Mannheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cognition: MMSE:	MMSE: Mini Mental State Examination; higher is better	after 28 weeks, i.e. end of Phase 2
Other	THINC-it:	THINC-it: Tool for Cognitive Assessment and Measurement; green - amber - red (red means lower than 1 standard deviation worse than healthy control subjects)	after 28 weeks, i.e. end of Phase 2
Primary	Time to relapse	Time to relapse (relapse defined as BPRS 20 % higher than individual BPRS at start of PHASE 2 at any following study visit OR any unscheduled readmission due to a worsening of psychiatric symptoms OR any unscheduled visit with an BPRS 20 % higher than individual BPRS at start of PHASE 2).	28 weeks (duration of PHASE 2)
Secondary	Number of relapse free subjects	Number of relapse free subjects at the end of PHASE 2	after 28 weeks, i.e. end of Phase 2
Secondary	BPRS	BPRS: Brief Psychiatric Rating scale; higher is worse	after 28 weeks, i.e. end of Phase 2
Secondary	GAF:	GAF: Global Assessment of Functioning; higher is better	after 28 weeks, i.e. end of Phase 2
Secondary	SLSSWB:	SLSSWB: self-labeling, stigma stress and well-being (SLSSWB); descriptive subscales	after 28 weeks, i.e. end of Phase 2
Secondary	PANSS:	PANSS: Positive and Negative Syndrome Scale; higher is worse	after 28 weeks, i.e. end of Phase 2
Secondary	HAMD:	HAMD: Hamilton Depression scale; higher is worse; SSMIS-SF: Self-Stigma of Mental Illness Scale - Short Form; descriptive subscales	after 28 weeks, i.e. end of Phase 2
Secondary	NCRS-dv:	NCRS-dv: Northoff catatonia rating scale (German version); higher is worse	after 28 weeks, i.e. end of Phase 2
Secondary	Q-LES-Q-18:	Q-LES-Q-18: Quality of Life Enjoyment and Satisfaction Questionnaire (for patients with schizophrenia); higher is better	after 28 weeks, i.e. end of Phase 2