Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 7 of 12 for:    pimozide

Antipsychotic Induced Structural and Functional Brain Changes (APIC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02435095
Recruitment Status : Recruiting
First Posted : May 6, 2015
Last Update Posted : December 22, 2017
Sponsor:
Information provided by (Responsible Party):
RWTH Aachen University

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.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: Maintenance treatment Drug: Intermittent treatment Phase 4

Detailed Description:

Patients with diagnosis of schizophrenia according to DSM-5 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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 544 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Are Antipsychotics Neurotoxic or Neuroprotective? A Long-term Comparison of Two Treatment Strategies
Study Start Date : May 2015
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : April 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arm Intervention/treatment
Active Comparator: Maintenance treatment (Control)
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

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).

Other Name: Antipsychotics

Experimental: Intermittent Treatment (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

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).

Other Name: Antipsychotics




Primary Outcome Measures :
  1. Total grey matter volume [ Time Frame: over 12 months ]
    change in total grey matter volume


Secondary Outcome Measures :
  1. Grey matter volume (hippocampus, prefrontal cortex) [ Time Frame: after 6 and 24 months ]
    change of volume

  2. Assessment of safety as assessed with the following instrument: EPS [ Time Frame: after 6 and 12 months ]
    Extrapyramidal symptom scale (EPS)

  3. Assessment of safety as assessed with the following instrument: BARS [ Time Frame: after 6 and 12 months ]
    Barnes Akathisia Rating Scale (BARS)

  4. Assessment of safety as assessed with the following instrument: Arizona Scale [ Time Frame: after 6 and 12 months ]
    Sexual function (Arizona Scale)

  5. Global assessment of safety as assessed with laboratory values [ Time Frame: after 6 and 12 months ]
    Metabolic side effects (Body mass index, HbA1c, Glucose, Cholesterol, Triglycerides)

  6. Cognition [ Time Frame: after 6 and 12 months ]
    Brief Assessment of Cognition in Schizophrenia (BACS)

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

  8. Psychopathology as assessed with the PANSS [ Time Frame: after 6 and 12 months ]
    Positive and Negative Syndrome Scale (PANSS)

  9. Psychopathology as assessed with the CGI [ Time Frame: after 6 and 12 months ]
    Clinical Global Impression (CGI)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02435095


Contacts
Layout table for location contacts
Contact: Sabrina Schaffrath 0049 241 80 ext 89821 saschaffrath@ukaachen.de
Contact: Sarah Lammertz, PhD 0049 241 80 ext 89821 slammertz@ukaachen.de

Locations
Layout table for location information
Germany
RWTH University Hospital Aachen Recruiting
Aachen, NRW, Germany, 52074
Contact: Sabrina Schaffrath       saschaffrath@ukaachen.de   
Contact: Sarah Lammertz       slammertz@ukaachen.de   
Alexianer Aachen GmbH Not yet recruiting
Aachen, Germany, 52062
Zentrum für Neurologie und Seelische Gesundheit im Kapuziner Karree Aachen Not yet recruiting
Aachen, Germany, 52062
Contact: Frank Bergmann, Dr. med.         
LVR Klinik Bonn Recruiting
Bonn, Germany, 53111
LVR Klinik Düren Not yet recruiting
Düren, Germany, 52353
Klinik und Poliklinik für Psychiatrie und Psychotherapie der Heinrich-Heine-Universität Düsseldorf Recruiting
Düsseldorf, Germany, 40629
LVR Klinik Essen Not yet recruiting
Essen, Germany, 45147
ViaNobis Gangelt Recruiting
Gangelt, Germany, 52538
Klinik Königshof (Abteilung für Allgemeine Psychiatrie) Recruiting
Krefeld, Germany, 47807
LVR Klinik Langenfeld Recruiting
Langenfeld, Germany, 40764
LVR Klinik Viersen Not yet recruiting
Viersen, Germany, 41749
Sponsors and Collaborators
RWTH Aachen University
Investigators
Layout table for investigator information
Principal Investigator: Klaus Mathiak, Univ.-Prof. Dr. Dr. Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital RWTH Aachen, Germany

Layout table for additonal information
Responsible Party: RWTH Aachen University
ClinicalTrials.gov Identifier: NCT02435095     History of Changes
Other Study ID Numbers: 13-082
First Posted: May 6, 2015    Key Record Dates
Last Update Posted: December 22, 2017
Last Verified: December 2017
Keywords provided by RWTH Aachen University:
Schizophrenia
Maintenance treatment, Intermittent treatment
Brain volume
Antipsychotics
Additional relevant MeSH terms:
Layout table for MeSH terms
Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs