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Aripiprazole Augmentation for Clozapine-Treated Patients With Refractory Schizophrenia

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: NCT00328367
Recruitment Status : Completed
First Posted : May 19, 2006
Last Update Posted : October 29, 2008
Korea Otsuka Pharmaceutical Co., Ltd.
Information provided by:
Seoul National University Hospital

Brief Summary:
The purpose of this study is to determine whether aripiprazole augmentation is safe and effective in the treatment of clozapine-treated patients with refractory schizophrenia.

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: aripiprazole Drug: placebo Phase 4

Detailed Description:

Clozapine is renowned for its efficacy in treating schizophrenia refractory to typical or atypical antipsychotics. Though the effectiveness of clozapine has been established, a considerable number of patients with schizophrenia are partially responsive or unresponsive to clozapine. In addition, long-term use of clozapine is associated with the development of obsessive-compulsive symptoms and metabolic syndrome. In order to overcome these short-comings and to increase efficacy, aripiprazole augmentation was implemented. Quantitative electroencephalogram will be used to monitor the occurrence of abnormal findings and to analyze the changes in electroencephalographic pattern with linear and non-linear methodology.

Comparisons: Design of double-blind randomized placebo controlled study of patients at Refractory Schizophrenia Clinique in Department of Neuropsychiatry at Seoul National University Hospital.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind Randomized Placebo Controlled Study of Aripiprazole Augmentation for Clozapine-Treated Patients With Refractory Schizophrenia
Study Start Date : December 2005
Actual Primary Completion Date : December 2006
Actual Study Completion Date : February 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arm Intervention/treatment
Experimental: A
clozapine plus aripiprazole
Drug: aripiprazole
aripiprazole augmentation of clozapine
Other Names:
  • abilify
  • OPC-14597

Placebo Comparator: B
clozapine plus placebo
Drug: placebo

Primary Outcome Measures :
  1. Brief Psychotic Rating Scale (BPRS): Measure of efficacy will be changes in BPRS total and subscale scores from baseline to 8th week endpoint. Follow-up evaluation will be made every 6th month till 1 year after 8th week end point. [ Time Frame: one year ]
  2. Schedule for Assessment of Negative Symptoms (SANS): Measure of efficacy will be changes in SANS total and subscale scores from baseline to 8th week endpoint. Follow-up evaluation will be made at 6 month and 12 month after 8th week end point. [ Time Frame: one year ]
  3. Serum Prolactin Level [ Time Frame: one year ]
  4. Body Mass Index & Abdominal Circumference [ Time Frame: one year ]
  5. Lipid Panel with LDL Cholesterol [ Time Frame: one year ]
  6. FBS-PP & HbA1c [ Time Frame: one year ]

Secondary Outcome Measures :
  1. Clinical Global Impression-Severity & Improvement (CGI-S & CGI-I) [ Time Frame: one year ]
  2. Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: one year ]
  3. Yale-Brown Obsessive Compulsive Scale (YBOCS) [ Time Frame: one year ]
  4. Subjective Well-being under Neuroleptics scale (SWN) [ Time Frame: one year ]
  5. Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) [ Time Frame: one year ]
  6. Udvalg Fur Kliniske Undersogesler (UKU) [ Time Frame: one year ]
  7. Blood Pressure and Pulse Rate [ Time Frame: one year ]
  8. Admission Battery, CBC, & EKG [ Time Frame: one year ]
  9. Serum Clozapine Level [ Time Frame: one year ]
  10. Quantitative Electroencephalogram [ Time Frame: one year ]

Information from the National Library of Medicine

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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:

  • Male or female patients, 18-65 years of age.
  • Patients must have a diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).
  • Female patients of menarche must be using a medically accepted means of contraception (e.g. oral contraceptives, Depo-Provera, abstinence).
  • Each patient must provide written informed consent after full explanation of study protocol, and authorized legal guardian must understand the nature of the study and must also give assent to study participation.
  • Patients must have a baseline (day 0) BPRS score of at least 35 or over 2 of 5 SANS global rating item scores of at least 3.
  • Patients have been receiving clozapine treatment for more than 1 year and there has been no change in clozapine dosage for more than 3 months.
  • Patients must have a history of antipsychotic treatment with at least 2 different kinds prior to clozapine administration.
  • Subjects who are fluent in Korean.

Exclusion Criteria:

  • DSM-IV substance (except nicotine or caffeine) dependence within the past 1 year.
  • Female patients who are either pregnant or lactating.
  • Mental retardation (IQ < 70).
  • Neurological disorders including epilepsy, stroke, or severe head trauma.
  • Clinically significant laboratory abnormalities, on any of the following tests: CBC with differential, electrolytes, BUN, creatinine, hepatic transaminases, urinalysis and EKG.
  • Prior history of aripiprazole non-response or intolerance.
  • BPRS score of < 35 and over 4 of 5 SANS global rating item scores of < 3.
  • Participation in a clinical trial of another investigational drug within 3 months (90 days) prior to study entry.
  • Treatment with an injectable depot neuroleptic within less than three dosing interval between the last depot neuroleptic injections and baseline (day 0).
  • History of electroconvulsive therapy within the past 3 months.
  • Subjects who are not fluent in Korean.

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): NCT00328367

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Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
Sponsors and Collaborators
Seoul National University Hospital
Korea Otsuka Pharmaceutical Co., Ltd.
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Principal Investigator: Yong Sik Kim, MD, PhD Seoul National University Hospital

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Yong Sik Kim/Professor, Seoul National University Hospital Identifier: NCT00328367    
Other Study ID Numbers: KYS-2006-05209
First Posted: May 19, 2006    Key Record Dates
Last Update Posted: October 29, 2008
Last Verified: April 2008
Keywords provided by Seoul National University Hospital:
Additional relevant MeSH terms:
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Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Antidepressive Agents
Psychotropic Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin 5-HT1 Receptor Agonists
Serotonin Receptor Agonists
Serotonin Agents
Serotonin 5-HT2 Receptor Antagonists
Serotonin Antagonists
Dopamine D2 Receptor Antagonists
Dopamine Antagonists
GABA Antagonists
GABA Agents