Trial document




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  DRKS00008018

Trial Description

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Title

Are Antipsychotics Neurotoxic or Neuroprotective? A Long-term Comparison of Two Treatment Strategies of Schizophrenia

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Trial Acronym

Antipsychotic Induced Brain Changes (APIC)

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URL of the Trial

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Brief Summary in Lay Language

Until now, functional and structural changes of the brain are considered to be the cause or result of a schizophrenic disease. However, numerous studies of the last years hypothesise that even the antipsychotic drug treatment might lead to structural changes in the brain, specifically grey matter loss (here are the cell bodies of the nerve cells located). Furthermore, a multi-year study in the Netherlands has shown that a stop of disease can be achieved more often in patients tapered off antipsychotic medication at an early stage. Under this study we will examine the question of to what extent a medical therapy of a schizophrenic disease contributes to structural and functional changes of the brain. Thus, these brain changes shall be investigated via MRI in a large-scale clinical study. This is an examination of the cranium without administration of a contrast agent. At first the brain structures of patients are interesting who are just getting ill and are treated with antipsychotics never before, but also all other patients with schizophrenia according to DSM-5, who would benefit from a possible randomization into the interval versus the long-term therapy arm and whose drug pretreatment is well documented. Besides one half of the patients will get an continuous antipsychotic medication after the first psychotic episode for at least 12 months (current clinical standard). The other half of patients are tapered off medication. The obtained findings about the disease shall make a long-term contribution to treat the disease more effective and with less adverse effects.
Based on BfArM's decision the APIC-Trial will now be conducted according to the German Drug Law (AMG). Reason for the Change is the interval therapy which is not considered Standard of care. Due to a re-submission at the ethics committee a new reference number was added. Moreover, the patient number was re-calculated due to participation of multiple centres.
On 21.11.2017 the BfArM approved the substantial amendment concerning the inclusion criteria of patients. All patients with schizophrenia according to DSM-5 can now be enrolled into the study; they do not have to deal with the first episode of schizophrenia.

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Brief Summary in Scientific Language

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. Longterm 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 we 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, we 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.

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Organizational Data

  •   DRKS00008018
  •   2015/04/24
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  •   yes
  •   Approved
  •   156/16, Ethik-Kommission an der Medizinischen Fakultät der RWTH Aachen
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Secondary IDs

  •   2016-001554-18 
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Health Condition or Problem studied

  •   F20 -  Schizophrenia
  •   DSM-IV 295: Schizophrenia
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Interventions/Observational Groups

  •   Maintenance treatment (control):
    Treatment with antipsychotic drug (type not specified) for at least 12 months
  •   Intermittent treatment (experimental):
    Treatment with antipsychotic drug (type not specified) 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.
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   assessor
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   IV
  •   No
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Primary Outcome

Total grey matter volume [Time Frame: after 12 months] comparing intermittent therapy with maintenance treatment via MRI examination at different measuring time points

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Secondary Outcome

• Grey matter volume (hippocampus, prefrontal cortex) [Time Frame: after 6 and 24 months]:
change of volume

• Assessment of safety [Time Frame: after 6 and 12 months]:
Drop-out rates, extrapyramidal side effects (ESRS (Extrapyramidal Symptoms Rating Scale), BARS (Barnes Akathisia Rating Scale)); sexual function (Arizona Scale);
metabolic side effects (BMI, HbA1c, Glucose, Cholesterol, Triglycerides)

• Cognition and psychopathology [Time Frame: after 6 and 12 months]:
BACS (Brief Assessment of Cognition in Schizophrenia) and PANSS (Positive and Negative Symptoms Scale), CGI (Clinical Global Impression-Skala)

• Quality of life change [Time Frame: after 6 and 12 months]:
SF-36 (Short Form-36 Health Survey), GAF (Global Assessment of Functioning Scale), visual analogue scales

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • other 
  • other 
  • Medical Center 
  • Medical Center 
  • Medical Center 
  • Medical Center 
  • other 
  • Medical Center 
  • Medical Center 
  • Medical Center 
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Recruitment

  •   Actual
  •   2015/06/25
  •   544
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   65   Years
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Additional Inclusion Criteria

• Patients with diagnosis of schizophrenia according to DSM-5
• Age 18-65 years
• Written informed consent prior to study participation
• Subjects being contractually and mentally capable to attend the medical staffs’ orders
• MRI capability

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Exclusion Criteria

• 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)

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Addresses

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    • RWTH Aachen
    • Ms.  Dr. med.  Susanne  Isfort 
    • Pauwelsstr. 30
    • 52074  Aachen
    • Germany
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    • Klinik für Psychiatrie,Psychotherapie und Psychosomatik, Uniklinik RWTH Aachen
    • Mr.  Univ.-Prof. Dr. med Dr. rer. nat.  Klaus  Mathiak 
    • Pauwelsstr. 30
    • 52074  Aachen
    • Germany
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    • Uniklinik RWTH Aachen
    • Ms.  Sabrina  Schaffrath 
    • Pauwelsstr. 30
    • 52074  Aachen
    • Germany
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    • Uniklinik RWTH Aachen
    • Ms.  Dr.  Sarah  Lammertz 
    • Pauwelsstr. 30
    • 52074  Aachen
    • Germany
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Sources of Monetary or Material Support

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    • Bundesministerium für Bildung und Forschung (BMBF) Dienstsitz Bonn
    • Heinemannstr. 2
    • 53175  Bonn
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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