Aripiprazole Augmentation for Clozapine-Treated Patients With Refractory Schizophrenia

This study has been completed.
Sponsor:
Collaborator:
Korea Otsuka Pharmaceutical Co.,Ltd.
Information provided by:
Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT00328367
First received: May 17, 2006
Last updated: October 28, 2008
Last verified: April 2008
  Purpose

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 Intervention Phase
Schizophrenia
Drug: aripiprazole
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Serum Prolactin Level [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • Body Mass Index & Abdominal Circumference [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • Lipid Panel with LDL Cholesterol [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • FBS-PP & HbA1c [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clinical Global Impression-Severity & Improvement (CGI-S & CGI-I) [ Time Frame: one year ] [ Designated as safety issue: No ]
  • Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: one year ] [ Designated as safety issue: No ]
  • Yale-Brown Obsessive Compulsive Scale (YBOCS) [ Time Frame: one year ] [ Designated as safety issue: No ]
  • Subjective Well-being under Neuroleptics scale (SWN) [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • Udvalg Fur Kliniske Undersogesler (UKU) [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • Blood Pressure and Pulse Rate [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • Admission Battery, CBC, & EKG [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • Serum Clozapine Level [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • Quantitative Electroencephalogram [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Enrollment: 61
Study Start Date: December 2005
Study Completion Date: February 2008
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00328367

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

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Yong Sik Kim/Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT00328367     History of Changes
Other Study ID Numbers: KYS-2006-05209
Study First Received: May 17, 2006
Last Updated: October 28, 2008
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Seoul National University Hospital:
schizophrenia
aripiprazole
clozapine

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Clozapine
Aripiprazole
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

ClinicalTrials.gov processed this record on August 26, 2014