Aripiprazole Augmentation for Clozapine-Treated Patients With Refractory Schizophrenia

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Study Design

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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

Arms and Interventions

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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; placebo

Outcome Measures

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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 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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Locations

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.

Investigators

Principal Investigator:	Yong Sik Kim, MD, PhD	Seoul National University Hospital

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Click here for detailed information about aripiprazole. 

Publications:

Rocha FL, Hara C. Benefits of combining aripiprazole to clozapine: three case reports. Prog Neuropsychopharmacol Biol Psychiatry. 2006 Aug 30;30(6):1167-9. Epub 2006 May 2.

Henderson DC, Kunkel L, Nguyen DD, Borba CP, Daley TB, Louie PM, Freudenreich O, Cather C, Evins AE, Goff DC. An exploratory open-label trial of aripiprazole as an adjuvant to clozapine therapy in chronic schizophrenia. Acta Psychiatr Scand. 2006 Feb;113(2):142-7.

Ziegenbein M, Sieberer M, Calliess IT, Kropp S. Combination of clozapine and aripiprazole: a promising approach in treatment-resistant schizophrenia. Aust N Z J Psychiatry. 2005 Sep;39(9):840-1.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Chang JS, Ahn YM, Park HJ, Lee KY, Kim SH, Kang UG, Kim YS. Aripiprazole augmentation in clozapine-treated patients with refractory schizophrenia: an 8-week, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2008 May;69(5):720-31.

Responsible Party:	Yong Sik Kim/Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier:	NCT00328367 History of Changes
Other Study ID Numbers:	KYS-2006-05209
First Posted:	May 19, 2006
Last Update Posted:	October 29, 2008
Last Verified:	April 2008

Keywords provided by Seoul National University Hospital:

schizophrenia; aripiprazole; clozapine

Additional relevant MeSH terms:

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Aripiprazole; Clozapine; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants	Physiological Effects of Drugs; Psychotropic Drugs; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; GABA Antagonists; GABA Agents