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

December 8, 2015 updated by: Amir Krivoy, Geha Mental Health Center

Clozapine Versus Amisulpride Versus Their Combination in the Treatment of Drug-resistant Schizophrenia Patients

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Petach-Tikva, Israel, 49000
        • Geha Mental Health Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change from baseline in Positive and Negative Syndrome Scale (PANSS)
Time Frame: 10, 20 weeks and endpoint
10, 20 weeks and endpoint

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Geha Mental Health Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2011

Primary Completion (Anticipated)

October 1, 2013

Study Registration Dates

First Submitted

October 2, 2011

First Submitted That Met QC Criteria

October 5, 2011

First Posted (Estimate)

October 7, 2011

Study Record Updates

Last Update Posted (Estimate)

December 9, 2015

Last Update Submitted That Met QC Criteria

December 8, 2015

Last Verified

December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GMCH-014-11

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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