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Clozapine Versus Amisulpride in Treatment-resistant Schizophrenia Patients (ClozAmi)

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. Read our disclaimer for details. Identifier: NCT01448499
Recruitment Status : Withdrawn
First Posted : October 7, 2011
Last Update Posted : December 9, 2015
Information provided by (Responsible Party):
Amir Krivoy, Geha Mental Health Center

Brief Summary:

Background: schizophrenia is a debilitating mental disorder affecting about 1% of the general population. About 30% of patients will not react to current drug treatment and defined as treatment-resistant schizophrenia patients (TRSP). The best studied therapeutic option for this population is clozapine therapy. Clozapine was shown to be effective than any other antipsychotic drug in TRSP. Moreover, augmentation of clozapine was not demonstrated to be more effective than clozapine monotherapy. Albeit Clozapine superiority in TRSP, its use may be involved with many adverse effects, some of them are life-threatening, and need for routine blood tests. Amisulpride is an atypical antipsychotic drug with a different mechanism of action than clozapine, with less adverse effects. No study compared directly amisulpride and clozapine in TRSP.

Study objective: to compare, for the first time, the broad clinical effectiveness of clozapine and amisulpride and their combination in TRSP.

Study Design: a clinical, prospective, naturalistic, randomized, comparative study simulating a real-world approach of clinical decision making.

Methods: a total of 140 TRSP will be recruited from a large regional mental health center. Participants will be randomized into two treatment groups (70 in each group): clozapine monotherapy and amisulpride monotherapy. Assessment will be done following 10 and 20 weeks of treatment. In case of treatment failure (insufficient clinical response or severe adverse effect) participants will be offered either to switch to clozapine treatment (for failed amisulpride treatment) or to augment clozapine with amisulpride (for failed clozapine monotherapy patients). Thereafter, participants will be followed-up for a year. Assessment will be made using clinician rated scales and self-completed questionnaires, rating the broad phenomenology of schizophrenia (psychosis, mood, anxiety, obsessive-compulsive, cognitive and quality of life) and drug-related adverse effects (objective and subjective).

Analysis: comparison of the effectiveness of the three treatment groups: amisulpride, clozapine and their combination, in the various dimensions of TRSP.

Condition or disease Intervention/treatment Phase
Schizophrenia Treatment Resistant Disorders Drug: Clozapine Drug: Amisulpride Drug: Clozapine+Amisulpride Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clozapine Versus Amisulpride Versus Their Combination in the Treatment of Drug-resistant Schizophrenia Patients
Study Start Date : October 2011
Estimated Primary Completion Date : October 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia
Drug Information available for: Clozapine

Arm Intervention/treatment
Experimental: Clozapine
Clozapine monotherapy
Drug: Clozapine
escalating dose of clozapine up to 900 mg/day

Experimental: Amisulpride
Amisulpride monotherapy
Drug: Amisulpride
escalating dose of amisulpride up to 800 mg/day

Experimental: Augmentation
Augmentation of clozapine with amisulpride
Drug: Clozapine+Amisulpride
augmentation of clozapine with amisulpride

Primary Outcome Measures :
  1. Change from baseline in Positive and Negative Syndrome Scale (PANSS) [ Time Frame: 10, 20 weeks and endpoint ]

Secondary Outcome Measures :
  1. Change from baseline in Clinical Global Impression - Severity (CGI-S) [ Time Frame: 10 , 20 weeks and endpoint ]
  2. Change from baseline in Beck Depression Inventory (BDI) [ Time Frame: 10 , 20 weeks and endpoint ]
  3. Change from baseline in Beck Anxiety Inventory (BAI) [ Time Frame: 10, 20 weeks and endpoint ]
  4. Change from baseline in Schizophrenia Quality of Life Scale (SQLS) [ Time Frame: 10, 20 weeks and endpoint ]
  5. Change from baseline in Simpson-Angus Scale (SAS) [ Time Frame: 5, 10, 15, 20 weeks, endpoint ]
  6. Change from baseline in Clozapine Adverse Effects Inventory (CAEI) [ Time Frame: 5, 10 ,15, 20 weeks, endpoint ]

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.

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

Inclusion Criteria:

  1. Confirmed diagnosis of schizophrenia according to DSM-IV-TR criteria
  2. Treatment-resistant schizophrenia, defined as: documented treatment failure (insufficient clinical response or severe adverse effects) of two antipsychotics (one of them should be atypical) for an adequate duration of 6 weeks and in a sufficient dose of at least 600 mg/day of chlorpromazine equivalent
  3. Age 18-65 years
  4. Basal PANSS > 75
  5. CGI-S >3
  6. Persistent positive psychotic symptoms, with rating scores of moderate or worse on at least two of four positive symptom items (delusions, conceptual disorganization, hallucinatory behavior, and suspiciousness/persecution) on Positive and Negative Syndrome Scale (PANSS).
  7. Competent and willing to provide written, informed consent

Exclusion Criteria:

  1. Patients with concomitant treatment with lithium, anticonvulsants, antidepressants
  2. Patients with underlying severe medical illness, such as cardiovascular disease, cerebrovascular disease, bone marrow suppression or epilepsy
  3. A previous trial of clozapine or amisulpride
  4. Any known contraindication for treatment with clozapine or amisulpride
  5. Any woman who is pregnant or planning a pregnancy, and any woman of child bearing potential unless using adequate contraception

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 identifier (NCT number): NCT01448499

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Geha Mental Health Center
Petach-Tikva, Israel, 49000
Sponsors and Collaborators
Geha Mental Health Center
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Responsible Party: Amir Krivoy, Senior psychiatrist, Geha Mental Health Center Identifier: NCT01448499    
Other Study ID Numbers: GMCH-014-11
First Posted: October 7, 2011    Key Record Dates
Last Update Posted: December 9, 2015
Last Verified: December 2015
Keywords provided by Amir Krivoy, Geha Mental Health Center:
treatment resistant
Additional relevant MeSH terms:
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Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
GABA Antagonists
GABA Agents
Dopamine Antagonists
Dopamine Agents
Antidepressive Agents, Second-Generation
Antidepressive Agents