Comparison of Antipsychotic Combination Treatment of Olanzapine and Amisulpride to Monotherapy (COMBINE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Heinrich-Heine University, Duesseldorf
Sponsor:
Information provided by (Responsible Party):
Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier:
NCT01609153
First received: May 23, 2012
Last updated: May 21, 2014
Last verified: May 2014
  Purpose

A study to examine whether an antipsychotic combination treatment of olanzapine and amisulpride is more effective than olanzapine and amisulpride alone.


Condition Intervention Phase
Schizophrenia
Schizoaffective Disorder
Drug: Olanzapine
Drug: Amisulpride
Drug: Olanzapine and Amisulpride
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Double-blind Controlled Trial to Assess the Benefits of Olanzapine and Amisulpride Combination Treatment in Acutely Ill Schizophrenia Patients. - COMBINE

Resource links provided by NLM:


Further study details as provided by Heinrich-Heine University, Duesseldorf:

Primary Outcome Measures:
  • Symptomatic improvement of schizophrenia after 8 weeks of treatment in comparison to time of inclusion of patient measured py Positive and Negative Symptom Scale (PANSS) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Whether there is a symptomatic improvement of schizophrenia after 8 weeks of treatment in comparison to time of inclusion of patient measured py Positive and Negative Symptom Scale (PANSS)


Secondary Outcome Measures:
  • Symptomatic improvement of schizophrenia after 16 weeks of treatment in comparison to time of inclusion of patient measured py PANSS total score reduction [ Time Frame: 16 weeks. ] [ Designated as safety issue: No ]
    To study whether a combination treatment of olanzapine and amisulpride show a PANSS total score reduction from baseline to week 16.

  • Symptomatic improvement of schizophrenia from baseline to week 2 up to week 16 measured by PANSS total score reduction. [ Time Frame: Every 2 weeks up to week 16. ] [ Designated as safety issue: No ]
    Whether a combination treatment of olanzapine and amisulpride show a PANSS total score reduction from baseline to every 2 weeks up to week 16.

  • PANSS total score reduction from baseline to week 2 as a predictor of the change after 8 weeks [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Whether a change of PANSS total score reduction from baseline to week 2 is a predictor of the change after 8 weeks

  • Serious adverse drug reactions [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
    Frequency and severity of serious adverse drug reactions

  • Change of clinical condition measured by Clinical Global Impression Scale (CGI scale) [ Time Frame: every 2 weeks from baseline up to week 16 ] [ Designated as safety issue: No ]
    Whether there is a change of clinical condition measured by Clinical Global Impression Scale (CGI scale)

  • Change of the subjective well-being measured by Subjective Wellbeing under Neuroleptics Scale (SWN-K) [ Time Frame: between week 0, 8, 16 ] [ Designated as safety issue: No ]
    Whether there is a change of the subjective well-being measured by Subjective Wellbeing under Neuroleptics Scale(SWN-K)


Estimated Enrollment: 399
Study Start Date: June 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Olanzapine or Placebo Drug: Amisulpride
200-800 mg milligram(s)per day for 16 weeks
Other Name: Amisulprid Hexal
Drug: Olanzapine and Amisulpride

Zyprexa:

Coated tablet 5-20 mg milligram(s) per day for 16 weeks

Amisulpride:

Coated tablet 200-800 mg milligram(s)per day for 16 weeks

Other Name: Zyprexa, Amisuprid Hexal
Active Comparator: Amisulpride or Placebo Drug: Olanzapine
Coated tablet 5-20 mg milligram(s) per day for 16 weeks
Other Name: Zyprexa
Drug: Olanzapine and Amisulpride

Zyprexa:

Coated tablet 5-20 mg milligram(s) per day for 16 weeks

Amisulpride:

Coated tablet 200-800 mg milligram(s)per day for 16 weeks

Other Name: Zyprexa, Amisuprid Hexal
Active Comparator: Olanzapine and Amisulpride Drug: Olanzapine
Coated tablet 5-20 mg milligram(s) per day for 16 weeks
Other Name: Zyprexa
Drug: Amisulpride
200-800 mg milligram(s)per day for 16 weeks
Other Name: Amisulprid Hexal

Detailed Description:

Polypharmacy in antipsychotic therapy is an important issue when treating patients with schizophrenia. It is not well confirmed that a combination of two antipsychotic drugs lead to therapeutic benefit in contrast to monotherapy. However there is a highly frequent practice of combining atypical non-clozapine treatment that could be due to potential benefits when seeking alternatives to a high rate of non-response in acute phase. Therefore there is a need for further trials of sufficient power to address efficacy and safety issues of this regimen. Combining two selected atypical drugs in a complementary way may minimize side-effects and enhance efficacy. In order to specify these advantages it is intend to examine approaches to combination treatment: Amisulpride and olanzapine show complementing receptor binding profiles and have shown to have efficacy and good tolerability when administered in combination in retrospective studies. The object of this trial is to study whether acutely ill patients with combination of amisulpride and olanzapine are more frequently in symptomatic remission after 8 weeks than those with olanzapine or amisulpride monotherapy.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with schizophrenia and schizoaffective disorder according to International Classification of Diseases (ICD-10);
  • age 18-65;
  • Positive and Negative Symptom Scale Total-Score ≥ 70 and two items of the positive symptom subscale ≥4.
  • voluntary treatment after written informed consent
  • legal capacity
  • exclusion of pregnancy by laboratory test (Beta HCG)

Exclusion Criteria:

  • participation in other interventional studies with drugs or medical devices
  • first episode patients
  • physical disease that might have effects on the conduct or evaluation of the trial
  • contraindications to medication according to experts information
  • oversensitivity to active substance or other component of the drugs used
  • known clozapine resistance
  • suicidal ideation
  • pregnancy or lactation
  • which of pregnancy or absence save contraception
  • dependency to sponsor or investigator
  • institutionalization through judicial or regulatory order
  • oversensitivity to placebo (mannite/aerosil)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01609153

Contacts
Contact: Joachim Cordes, Dr. 0049 211 922 ext 3402 joachim.cordes@lvr.de
Contact: Sandra Feyerabend 0049211922 ext 2796 sandra.feyerabend@lvr.de

Locations
Germany
RWTH Aachen Recruiting
Aachen, Germany, 52074
Contact: Gerhardt Gründer, Prof. Dr.    +49-241-8089 ext 821    ggruender@ukaachen.de   
Contact: André Kirner-Veselinovic, Dr.    +49-241-8089 ext 539    akirner@ukaachen.de   
Bezirkskliniken Schwaben, Bezirkskrankenhaus Augsburg Recruiting
Augsburg, Germany, 89156
Contact: Susanne Stübner, Dr.    +49-0821-4803 ext 1021      
Contact: Jessica Baumgärtner, Dr.    +49-0821-4803 ext 0      
LVR-Klinikum Düsseldorf Recruiting
Düsseldorf, Germany, 40629
Contact: Joachim Cordes, Dr.    0049211922 ext 3402    joachim.cordes@lvr.de   
Contact: Christian Schmidt-Kraepelin, Dr.    0049211922 ext 3535    christian.schmidt-kraepelin@lvr.de   
Klinik für Psychiatrie, Psychotherapie und Psychosomatik am Bezirkskrankehaus Günzburg Recruiting
Günzburg, Germany, 89312
Contact: Markus Jäger, Dr.    0049822196 ext 2204    markus.jaeger@bkh-guenzburg.de   
Contact: Karel Frasch, Dr.    00498221196 ext 00    karel.frasch@bkh-guenzburg.de   
LVR-Klinikum Köln Recruiting
Köln, Germany, 51109
Contact: Dirk Reske, Dr.    00492218993 ext 797    dirk.reske@lvr.de   
Contact: Ulrike Reinholz, Dr.    00492218993 ext 0    ulrike.reinholz@lvr.de   
LVR-Klinik Langenfeld Recruiting
Langenfeld, Germany, 40764
Contact: Andrea Neff, Dr.    00492173102 ext 0    andrea.neff@lvr.de   
Contact: Martina Pellio-Blume, Dr.    00492173102 ext 0    martina.pellio-blume@lvr.de   
Universitätsklinikum Leipzig, Klinik und Poliklinik für Psychiatrie und Psychotherapie Recruiting
Leipzig, Germany, 04103
Contact: Michael Kluge, Dr    00493419724 ext 673    michael.kluge@medizin.uni-leipzig.de   
Contact: Jens Dietzel, Dr.    00493419724 ext 530    jens.dietzel@medizin.uni-leipzig.de   
Universitätsmedizin Mainz Klinik für Psychiatrie und Psychotherapie Recruiting
Mainz, Germany, 55131
Contact: Andreas Konrad, Dr.    +496131 ext 7340    andreas.konrad@unimedizin-mainz.de   
Contact: Nadine Dreimüller, Dr.       nadine.dreimueller@unimedizin-mainz.de   
Zentralinstitut für Seelische Gesundheit Recruiting
Mannheim, Germany, 68159
Contact: Matthias Zink, Professor    0049-0621-1703 ext 2911    Matthias.zink@zi-mannheim.de   
Contact: Susanne Englisch, Dr.    0049-0621-1703 ext 2525    Susanne.englisch@zi-mannheim.de   
TU München Recruiting
München, Germany, 81675
Contact: Stefan Leucht, Prof. Dr.    +49-89-4140 ext 4249    stefan.leucht@lrz.tu-muenchen.de   
Contact: Stephan Heres, PD Dr.    +49-89-4140 ext 4249    s.heres@lrz.tu-muenchen.de   
LMU München Recruiting
München, Germany, 80336
Contact: Peter Falkai, Pro. Dr.    +49-89-5160 ext 5501    Peter.Falkai@med.uni-muenchen.de   
Contact: Berend Malchow, Dr.       Berend.Malchow@med.uni-muenchen.de   
Bezirksklinikum Regensburg, Klinik für Psychiatrie und Psychotherapie Recruiting
Regensburg, Germany, 93053
Contact: Thomas Frodl, Professor    0049941941 ext 0    thomas.frodl@medbo.de   
Contact: Elmar Frank, Dr.    0049941941 ext 0    elmar.frank@medbo.de   
Sponsors and Collaborators
Heinrich-Heine University, Duesseldorf
Investigators
Principal Investigator: Cordes Joachim, Dr. Heinrich-Heine University, Duesseldorf
  More Information

No publications provided

Responsible Party: Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier: NCT01609153     History of Changes
Other Study ID Numbers: COMBINE
Study First Received: May 23, 2012
Last Updated: May 21, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Heinrich-Heine University, Duesseldorf:
schizophrenia
amisulpride
olanzapine
polypharmacy

Additional relevant MeSH terms:
Psychotic Disorders
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Sultopride
Sulpiride
Olanzapine
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antidepressive Agents, Second-Generation
Antidepressive Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Serotonin Agents

ClinicalTrials.gov processed this record on August 28, 2014