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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 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: July 1, 2015
Last verified: July 2015
  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: August 2017
Estimated Primary Completion Date: August 2016 (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-(0)241-8089 ext 821    ggruender@ukaachen.de   
Contact: André Kirner-Veselinovic, Dr.    +49-(0)241-8089 ext 539    akirner@ukaachen.de   
Rheinhessen Fachklinik Alzey Recruiting
Alzey, Germany, 55232
Contact: Anke Brockhaus-Dumke, PD Dr.    +49-(0)6731 ext 501593    a.brockhaus-dumke@rfk.landeskrankenhaus.de   
Contact: Stephan Quirrenbach, Dr.       s.quirrenbach@rfk.landeskrankenhaus.de   
Bezirkskliniken Schwaben, Bezirkskrankenhaus Augsburg Recruiting
Augsburg, Germany, 89156
Contact: Susanne Stübner, Dr.    +49-0821-4803 ext 1021    Susanne.Stuebner@bkh-augsburg.de   
Contact: Marianne Bärhold, Dr.    +49-0821-4803 ext 0    Marianne.baerhold@bkh-augsburg.de   
Charite-Universitätsmedizin Berlin Recruiting
Berlin, Germany, 10117
Contact: Walter de Milles, Dr.    +49-(0)30-450617238    Walter.deMillas@charite.de   
Contact: Christian Müller, Dr.       christian.mueller@charite.de   
LWL-Klinik Dortmund Not yet recruiting
Dortmund, Germany, 44281
Contact: Hans-Jörg Assion, Prof. Dr.    +49-(0)231-45092673    hans-joerg.assion@wkp-wl.org   
Contact: Gerhard Reymann, PD Dr.       gerhard.reymann@lwl.org   
LVR-Klinikum Düsseldorf Recruiting
Düsseldorf, Germany, 40629
Contact: Joachim Cordes, Dr.    +49-(0)211-922 ext 3402    joachim.cordes@lvr.de   
Contact: Christian Schmidt-Kraepelin, Dr.    +49-(0)211-922 ext 3535    christian.schmidt-kraepelin@lvr.de   
Universitätsmedizin Göttingen Not yet recruiting
Göttingen, Germany, 37075
Contact: Bernhard Kis, Dr.    +49-(0)551-3910114    Bernhard.Kis@med.uni-goettingen.de   
Contact: David Zilles, Dr.       dzilles@gwdg.de   
Klinik für Psychiatrie, Psychotherapie und Psychosomatik am Bezirkskrankehaus Günzburg Suspended
Günzburg, Germany, 89312
Universitätsklinikum Heidelberg Not yet recruiting
Heidelberg, Germany, 69115
Contact: Daniela Roesch Ely, PD Dr.    +49-(0)6221-567227    Daniela.Roesch@med.uni-heidelberg.de   
Contact: Sibylle Häfner, PD Dr.       sybille.haefner@med.uni-heidelberg.de   
LVR-Klinikum Köln Recruiting
Köln, Germany, 51109
Contact: Dirk Reske, Dr.    +49-(0)2218993 ext 797    dirk.reske@lvr.de   
Contact: Ulrike Reinholz, Dr.    +49-(0)2218993 ext 0    ulrike.reinholz@lvr.de   
LVR-Klinik Langenfeld Recruiting
Langenfeld, Germany, 40764
Contact: Andrea Neff, Dr.    +49-(0)2173102 ext 0    andrea.neff@lvr.de   
Contact: Martina Pellio-Blume, Dr.    +49-(0)2173102 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: Nadine Dreimüller, Dr.    +49-(0)6131 ext 7340    nadine.dreimueller@unimedizin-mainz.de   
Contact: Bao Khang Dreimüller, Dr.       bao-khang.dreimueller@unimedizin-mainz.de   
Zentralinstitut für Seelische Gesundheit Recruiting
Mannheim, Germany, 68159
Contact: Matthias Zink, Professor    +49-(0)621-1703 ext 2911    Matthias.zink@zi-mannheim.de   
Contact: Susanne Englisch, Dr.    +49-(0)621-1703 ext 2525    Susanne.englisch@zi-mannheim.de   
LMU München Recruiting
München, Germany, 80336
Contact: Peter Falkai, Pro. Dr.    +49-(0)89-5160 ext 5501    Peter.Falkai@med.uni-muenchen.de   
Contact: Berend Malchow, Dr.       Berend.Malchow@med.uni-muenchen.de   
TU München Suspended
München, Germany, 81675
Bezirksklinikum Regensburg, Klinik für Psychiatrie und Psychotherapie Recruiting
Regensburg, Germany, 93053
Contact: Thomas Frodl, Professor    +49-(0)941941 ext 0    thomas.frodl@medbo.de   
Contact: Elmar Frank, Dr.    +49-(0)941941 ext 0    elmar.frank@medbo.de   
Universitätsklinikum Würzburg Not yet recruiting
Würzburg, Germany, 97080
Contact: Gerald Stöber, Prof. Dr.    +49-(0)931-20176050    Stoeber_G@ukw.de   
Contact: Micha Gawlik, Dr.       gawlik_M@ukw.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: July 1, 2015
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
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Olanzapine
Sulpiride
Sultopride
Antidepressive Agents
Antidepressive Agents, Second-Generation
Antiemetics
Antipsychotic Agents
Autonomic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on September 01, 2015