NCT01448499

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.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2011

Completed
1 day until next milestone

First Submitted

Initial submission to the registry

October 2, 2011

Completed
5 days until next milestone

First Posted

Study publicly available on registry

October 7, 2011

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2013

Completed
Last Updated

December 9, 2015

Status Verified

December 1, 2015

Enrollment Period

2 years

First QC Date

October 2, 2011

Last Update Submit

December 8, 2015

Conditions

Keywords

schizophreniaclozapineamisulpridecombinationtreatment resistant

Outcome Measures

Primary Outcomes (1)

  • Change from baseline in Positive and Negative Syndrome Scale (PANSS)

    10, 20 weeks and endpoint

Secondary Outcomes (6)

  • 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

  • +1 more secondary outcomes

Study Arms (3)

Clozapine

EXPERIMENTAL

Clozapine monotherapy

Drug: Clozapine

Amisulpride

EXPERIMENTAL

Amisulpride monotherapy

Drug: Amisulpride

Augmentation

EXPERIMENTAL

Augmentation of clozapine with amisulpride

Drug: Clozapine+Amisulpride

Interventions

escalating dose of clozapine up to 900 mg/day

Clozapine

escalating dose of amisulpride up to 800 mg/day

Amisulpride

augmentation of clozapine with amisulpride

Augmentation

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Geha Mental Health Center

Petah Tikva, 49000, Israel

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

ClozapineAmisulpride

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic DisordersMental Disorders

Intervention Hierarchy (Ancestors)

DibenzazepinesHeterocyclic Compounds, 3-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsBenzamidesAmidesOrganic ChemicalsBenzoatesAcids, CarbocyclicCarboxylic AcidsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbons
0

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Senior psychiatrist

Study Record Dates

First Submitted

October 2, 2011

First Posted

October 7, 2011

Study Start

October 1, 2011

Primary Completion

October 1, 2013

Last Updated

December 9, 2015

Record last verified: 2015-12

Locations