NCT02435095

Brief 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 hypothesize that intermittent treatment (experimental) with antipsychotics, which is directed exclusively against the positive symptoms of Schizophrenia, is associated with less loss in total grey matter volume than maintenance treatment (control). 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.The aim of the present study is to compare two different drug therapies -maintenance therapy versus on-demand, intermittent therapy- in terms of their treatment's success and the structural changes in the brain.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
174

participants targeted

Target at P75+ for phase_4 schizophrenia

Timeline
Completed

Started May 2015

Longer than P75 for phase_4 schizophrenia

Geographic Reach
1 country

11 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 14, 2015

Completed
17 days until next milestone

Study Start

First participant enrolled

May 1, 2015

Completed
5 days until next milestone

First Posted

Study publicly available on registry

May 6, 2015

Completed
5.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2020

Completed
Last Updated

November 25, 2020

Status Verified

November 1, 2020

Enrollment Period

5.3 years

First QC Date

April 14, 2015

Last Update Submit

November 23, 2020

Conditions

Schizophrenia

Keywords

SchizophreniaMaintenance treatment, Intermittent treatmentBrain volumeAntipsychotics

Outcome Measures

Primary Outcomes (1)

  • Total grey matter volume

    change in total grey matter volume

    over 12 months

Secondary Outcomes (9)

  • Grey matter volume (hippocampus, prefrontal cortex)

    after 6 and 24 months

  • Assessment of safety as assessed with the following instrument: EPS

    after 6 and 12 months

  • Assessment of safety as assessed with the following instrument: BARS

    after 6 and 12 months

  • Assessment of safety as assessed with the following instrument: Arizona Scale

    after 6 and 12 months

  • Global assessment of safety as assessed with laboratory values

    after 6 and 12 months

  • +4 more secondary outcomes

Study Arms (2)

Maintenance treatment (Control)

ACTIVE COMPARATOR

287 female and male patients with 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).

Drug: Maintenance treatment

Intermittent Treatment (Experimental)

EXPERIMENTAL

287 female and male patients with 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).

Drug: Intermittent treatment

Interventions

Maintenance treatmentDRUG

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).

Also known as: Antipsychotics
Maintenance treatment (Control)
Intermittent treatmentDRUG

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).

Also known as: Antipsychotics
Intermittent Treatment (Experimental)

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with diagnosis of schizophrenia according to DSM-5
  • Age 18-65 years
  • Written declaration of consent
  • Subjects being contractually and mentally capable to attend the medical staffs' orders.
  • MRI capability

You may not qualify if:

  • Relevant somatic diseases, which could have an impact on the conduct of the study based on clinical judgement of the treating physician (e.g. epilepsy, cancer)
  • Prior insufficiently documented drug therapy with antipsychotics
  • Magnetic metals in and on the body, cardiac pacemakers and body piercings.
  • Pregnancy or lactation
  • Hospitalization of the patient ordered by the court or public authorities
  • Relationship of dependence or employment to sponsor or investigator
  • Simultaneous participation in another clinical trial (participation in an APIC subproject excluded)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

RWTH University Hospital Aachen

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Alexianer Aachen GmbH

Aachen, 52062, Germany

Location

Zentrum für Neurologie und Seelische Gesundheit im Kapuziner Karree Aachen

Aachen, 52062, Germany

Location

LVR Klinik Bonn

Bonn, 53111, Germany

Location

LVR Klinik Düren

Düren, 52353, Germany

Location

Klinik und Poliklinik für Psychiatrie und Psychotherapie der Heinrich-Heine-Universität Düsseldorf

Düsseldorf, 40629, Germany

Location

LVR Klinik Essen

Essen, 45147, Germany

Location

ViaNobis Gangelt

Gangelt, 52538, Germany

Location

Klinik Königshof (Abteilung für Allgemeine Psychiatrie)

Krefeld, 47807, Germany

Location

LVR Klinik Langenfeld

Langenfeld, 40764, Germany

Location

LVR Klinik Viersen

Viersen, 41749, Germany

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Opiate Substitution TreatmentAntipsychotic Agents

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Drug TherapyTherapeuticsTranquilizing AgentsCentral Nervous System DepressantsPhysiological Effects of DrugsPharmacologic ActionsChemical Actions and UsesCentral Nervous System AgentsTherapeutic UsesPsychotropic Drugs

Study Officials

  • Klaus Mathiak, Univ.-Prof. Dr. Dr.

    Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital RWTH Aachen, Germany

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 14, 2015

First Posted

May 6, 2015

Study Start

May 1, 2015

Primary Completion

August 1, 2020

Study Completion

August 1, 2020

Last Updated

November 25, 2020

Record last verified: 2020-11

Locations

DE(11)