Overview

This trial is active, not recruiting.

Condition schizophrenia
Treatments maintenance treatment, intermittent treatment
Phase phase 4
Sponsor RWTH Aachen University
Start date May 2015
End date September 2018
Trial size 544 participants
Trial identifier NCT02435095, 13-082

Summary

Continuation of antipsychotic drug treatment for at least 12 months after remission of the first psychotic episode represents the gold clinical standard, and it is recommended by all international treatment guidelines. Numerous studies have shown that the risk of relapse is significantly increased, if drug treatment is terminated prematurely. However, only a minority of patients achieve functional remission, even if they fully comply with treatment. Long-term adverse effects of the currently available drugs, specifically brain grey matter loss and development of supersensitivity psychosis, might outweigh their benefits. Thus, the current standard of long-term maintenance antipsychotic treatment, which has the primary goal of relapse prevention, has to be questioned. Here the investigators hypothesise that intermittent antipsychotic treatment (targeted exclusively at positive symptoms) initiated after the first psychotic episode is associated with less regional and global brain (grey matter) volume loss over a period of twelve months than continuous antipsychotic treatment. Furthermore, the investigators hypothesise that this targeted treatment approach is associated with better functional outcome (fewer negative symptoms, better cognitive performance, better quality of life) than continuous antipsychotic treatment,although the latter is initially associated with fewer relapses.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking single blind (outcomes assessor)
Primary purpose treatment
Arm
(Active Comparator)
287 female and male patients with first episode schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders- V (DSM-V) will be directed randomly to the maintenance treatment group (control). Patients will be treated according to the current clinical standard of long-term maintenance antipsychotic treatment. Study related procedures include safety assessments (physical examination, questionaires), laboratory assessments (blood sampling, urine analysis), efficacy assessments (questionaires) and volumetric Magnetic Resonance Imaging (structural MRI incl. volumetry). Study procedures are the same for both study groups (control/experimental).
maintenance treatment Antipsychotics
Treatment with antipsychotic drug (either second-generation antipsychotics or low-dose first generation antipsychotics) for at least 12 months. All antipsychotics approved in Germany are permitted (amisulpride, aripiprazole, benperidol, bromperidol, chlorprothixene, clozapine, flupentixole, fluphenazine, fluspirilene, haloperidol, levomepromazine, loxapine, lurasidone, melperone, olanzapine, paliperidone, perazine, perphenazine, pimozide, pipamperone, prothipendyl, quetiapine, risperidone, sertindole, sulpiride, thioridazine, ziprasidone, zuclopenthixole).
(Experimental)
287 female and male patients with first episode schizophrenia according to DSM-V will be directed randomly to the intermittent treatment group (experimental). Patients directed to this group will be tapered off medication. Study related procedures include safety assessments (physical examination, questionaires), laboratory assessments (blood sampling, urine analysis), efficacy assessments (questionaires) and volumetric Magnetic Resonance Imaging (structural MRI incl. volumetry). Study procedures are the same for both study groups (control/experimental).
intermittent treatment Antipsychotics
Treatment with antipsychotic drug (either second-generation antipsychotics or low-dose first generation antipsychotics) only for first episode of schizophrenia, tapering-off medication after remission of positive symptoms, reinstatement of treatment only in case of recurrence of positive symptoms. All antipsychotics approved in Germany are permitted (amisulpride, aripiprazole, benperidol, bromperidol, chlorprothixene, clozapine, flupentixole, fluphenazine, fluspirilene, haloperidol, levomepromazine, loxapine, lurasidone, melperone, olanzapine, paliperidone, perazine, perphenazine, pimozide, pipamperone, prothipendyl, quetiapine, risperidone, sertindole, sulpiride, thioridazine, ziprasidone, zuclopenthixole).

Primary Outcomes

Measure
Total grey matter volume
time frame: over 12 months

Secondary Outcomes

Measure
Grey matter volume (hippocampus, prefrontal cortex)
time frame: after 6 and 24 months
Assessment of safety as assessed with the following instrument: EPS
time frame: after 6 and 12 months
Assessment of safety as assessed with the following instrument: BARS
time frame: after 6 and 12 months
Assessment of safety as assessed with the following instrument: Arizona Scale
time frame: after 6 and 12 months
Global assessment of safety as assessed with laboratory values
time frame: after 6 and 12 months
Cognition
time frame: after 6 and 12 months
Quality of life
time frame: after 6 and 12 months
Psychopathology as assessed with the PANSS
time frame: after 6 and 12 months
Psychopathology as assessed with the CGI
time frame: after 6 and 12 months

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

Inclusion Criteria: - Patients with first-episode of schizophrenia according to DSM-V - aged between18 and 65 years - written informed consent prior to study participation - Subjects who are contractually capable and mentally able to understand and follow the instructions of the study personnel - Subjects eligible for MRI Exclusion Criteria: - The subject has a history of any other illness, which, in the opinion of the investigator, might have an effect on the study performance (e.g. malignant disease, epilepsia) - previous treatment with antipsychotics prior to study participation - magnetizable metal parts in or at the body, pacemakers, piercings - pregnant and lactating females - subject has been committed to an institution by legal or regulatory order - dependency or working relationship with the investigator - participation in a parallel interventional clinical study

Additional Information

Official title Are Antipsychotics Neurotoxic or Neuroprotective? A Long-term Comparison of Two Treatment Strategies
Principal investigator Gerhard Gründer, Prof., MD
Description All patients with the first episode of schizophrenia admitted to a hospital participating in the consortium will undergo magnetic resonance imaging (MRI) as soon as possible after admission. Ideally, this procedure is performed before initiation of antipsychotic treatment (benzodiazepines are allowed). If not possible for clinical reasons, antipsychotic treatment will be started and the MRI will be acquired within three days of initiation of drug treatment. The choice of the antipsychotic will be made by the treating physician. All approved antipsychotics are permitted, including first-generation antipsychotics such as haloperidol or flupenthixol. This is based on the recommendation of the British NICE guidelines: "In nine randomized controlled trials (RCTs) with a total of 1,801 participants with first-episode or early schizophrenia (including people with a recent onset of schizophrenia and people who have never been treated with antipsychotic medication), the evidence suggested there were no clinically significant differences in efficacy between the antipsychotic drugs examined." (NICE 2009, p. 105). However, since second-generation antipsychotics (SGA) are now considered first-line treatment for schizophrenia according to the German S3 guideline, it can be assumed that more than 80% of all patients will be treated with an SGA. As soon as positive symptoms are sufficiently controlled, medication will be completely tapered off within four weeks. Sufficient control of positive symptoms will defined as follows: "delusions" (Positive and Negative Syndrome Scale (PANSS) item 1), "hallucinatory behaviour" (PANSS item 3), and "suspiciousness/persecution" (PANSS item 6) have to be "absent" or "mild" (scores 1 or 2). The PANSS Positive score (7 items) must not be above 18. Patients in the experimental group who will not reach remission according to this definition will be switched to another antipsychotic according to clinical standards. Tapering of medication might be considered at a later time-point. Patients who cannot be tapered off medication will be treated with the lowest possible dose. Treatment of subsequent exacerbations / psychotic relapses will follow the same rules.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by RWTH Aachen University.