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

Central Institute of Mental Health, Mannheim

Status: Enrolling

Conditions: Treatment Resistant Schizophrenia; Schizophrenia

Treatments: Device: maintenance electroconvulsive therapy (mECT)

Study type: Interventional

Funder types: Other

Identifiers

NCT06456983

01KG2401 (Other Grant/Funding Number)

MECT-RESIST

Details and patient eligibility

About

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.

Full 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.

Enrollment: 140 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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140 participants in 2 patient groups

treatment as usual (TAU)

No Intervention group

Description:

Patients randomized to TAU only will continue on a stable drug regime for the next 28 weeks, but will not receive maintenance electroconvulsive therapy (mECT)

maintenance electroconvulsive therapy (mECT) plus TAU

Active Comparator group

Description:

All subjects will enter PHASE 1 and will receive a full course of routine ECT (maximum of 6 weeks and 3 treatments per week) while being on stable antipsychotic medication. All ECT-responders (patients with improvement of 30% or more on Brief Psychiatric Rating Scale (BPRS) will enter PHASE 2 and will be randomly assigned to the active comparator (mECT plus treatment-as-usual, TAU) or the control intervention (TAU) which both last 28 weeks. Non-responders (patients without improvement of at least 30 % on BPRS scale) will not enter PHASE 2.

Treatment:

Device: maintenance electroconvulsive therapy (mECT)