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

This study is currently recruiting participants.
Verified December 2012 by Geha Mental Health Center
Sponsor:
Information provided by (Responsible Party):
Amir Krivoy, Geha Mental Health Center
ClinicalTrials.gov Identifier:
NCT01448499
First received: October 2, 2011
Last updated: December 4, 2012
Last verified: December 2012
History of Changes
  Purpose

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 Intervention
Schizophrenia
Treatment Resistant Disorders
 Drug: Clozapine
Drug: Amisulpride
Drug: Clozapine+Amisulpride

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clozapine Versus Amisulpride Versus Their Combination in the Treatment of Drug-resistant Schizophrenia Patients

Resource links provided by NLM:

Drug Information available for: Clozapine
U.S. FDA Resources

Further study details as provided by Geha Mental Health Center:

Primary Outcome Measures:
  • Change from baseline in Positive and Negative Syndrome Scale (PANSS) [ Time Frame: 10, 20 weeks and endpoint ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in Clinical Global Impression - Severity (CGI-S) [ Time Frame: 10 , 20 weeks and endpoint ] [ Designated as safety issue: No ]
  • Change from baseline in Beck Depression Inventory (BDI) [ Time Frame: 10 , 20 weeks and endpoint ] [ Designated as safety issue: No ]
  • Change from baseline in Beck Anxiety Inventory (BAI) [ Time Frame: 10, 20 weeks and endpoint ] [ Designated as safety issue: No ]
  • Change from baseline in Schizophrenia Quality of Life Scale (SQLS) [ Time Frame: 10, 20 weeks and endpoint ] [ Designated as safety issue: No ]
  • Change from baseline in Simpson-Angus Scale (SAS) [ Time Frame: 5, 10, 15, 20 weeks, endpoint ] [ Designated as safety issue: Yes ]
  • Change from baseline in Clozapine Adverse Effects Inventory (CAEI) [ Time Frame: 5, 10 ,15, 20 weeks, endpoint ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 140
Study Start Date: October 2011
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

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

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01448499

Contacts
Contact: Amir Krivoy, M.D. 972-3-9258230 akrivoy@clalit.org.il

Locations
Israel
Geha Mental Health Center Recruiting
Petach-Tikva, Israel, 49000
Sponsors and Collaborators
Geha Mental Health Center
  More Information

No publications provided

Responsible Party: Amir Krivoy, Senior psychiatrist, Geha Mental Health Center
ClinicalTrials.gov Identifier: NCT01448499     History of Changes
Other Study ID Numbers: GMCH-014-11
Study First Received: October 2, 2011
Last Updated: December 4, 2012
Health Authority: Israel: Ministry of Health

Keywords provided by Geha Mental Health Center:
schizophrenia
clozapine
amisulpride
combination
treatment resistant

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

ClinicalTrials.gov processed this record on May 16, 2013