ClozAmi: Clozapine Versus Amisulpride in Treatment-resistant Schizophrenia Patients

Sponsor

Geha Mental Health Center (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01448499

Collaborator

(none)

Enrollment

Location

Arms

Study Details

Study Description

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	N/A

Study Design

Study Type:

Interventional

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 :

Oct 1, 2011

Anticipated Primary Completion Date :

Oct 1, 2013

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change from baseline in Positive and Negative Syndrome Scale (PANSS) [10, 20 weeks and endpoint]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Confirmed diagnosis of schizophrenia according to DSM-IV-TR criteria
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
Age 18-65 years
Basal PANSS > 75
CGI-S >3
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).
Competent and willing to provide written, informed consent

Exclusion Criteria:

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