Oxcarbazepine as an Adjunct of Antipsychotic Therapy in Acute Schizophrenia (OXC-SCZ)

This study has been completed.
Sponsor:
Information provided by:
University of Cologne
ClinicalTrials.gov Identifier:
NCT00637234
First received: March 10, 2008
Last updated: July 23, 2008
Last verified: July 2008
  Purpose

Over recent years an approach with the adjunctive administration of various anticonvulsant drugs has been discussed and a limited number of open and controlled studies were performed for carbamazepine, valproic acid, and lamotrigine. While the latter shows promising effects in the long run it has some handling difficulties in the acute treatment of acute psychotic exacerbations. Valproic acid has shown inconsistent effects in schizophrenia with no significant effects in a recent controlled study. Although still controversially discussed, carbamazepine was found to offer beneficial effects in the treatment of schizophrenia. Nonetheless, data on these effects are limited by small sample sizes or poor design of most of the respective studies. Furthermore, the complex pharmacological interactions of new atypical neuroleptics with carbamazepine underline the necessity of alternative strategies in adjuvant treatment of schizophrenia as well as in combined treatment of bipolar disorders with mood stabilizers and neuroleptics.

Oxcarbazepine (OXC) is a new anticonvulsant drug that acts as a pro-drug for the 10-monohydroxy metabolite (MHD), an active metabolite also of carbamazepine that is suggested to be responsible for most of its therapeutic actions. Therefore, the pharmacological action of OXC is very well comparable to carbamazepine whilst there are fewer unwanted side effects of OXC regarding eg. skin rush, and effects on blood compounds or cardiotropic effects.

The effects of OXC on cytochrome CYP3A4 and CYP3A5 are moderate and UDPGT is only slightly affected by OXC, which leads to less interaction with other compounds on a pharmacokinetical level.

In psychiatry, the few studies published until now report positive effects of OXC in bipolar disorders. With regards to our own clinical observations, OXC has shown potential beneficial effects as an adjunct in the treatment of schizophrenia as well that require further evaluation in a controlled study design.


Condition Intervention Phase
Schizophrenia
Drug: Oxcarbazepine
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Oxcarbazepine as an Adjunct of Antipsychotic Therapy in Acute Schizophrenia

Resource links provided by NLM:


Further study details as provided by University of Cologne:

Primary Outcome Measures:
  • Amount of Olanzapine Co-medication [ Time Frame: 5 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • BPRS [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Extrapyramidal symptoms [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  • Weight gain [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  • Prolactin levels in plasma [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  • ECG QT-C time elongation [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  • Neurocognitive performance [ Time Frame: 6 week ] [ Designated as safety issue: No ]

Enrollment: 54
Study Start Date: July 2004
Study Completion Date: July 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Oxcarbazepine
Oxcarbazepine (OXC), 300 mg tablets, up to 600 mg three times daily
Other Names:
  • Trileptal FCT 300MG.002
  • Film-coated tablet
  • Batch No.: X208 0802
  • Code: 3750031.002
  • Date of manufacture: September 2002
  • Date of evaluation: May 2004
Placebo Comparator: 2 Drug: Placebo
Placebo, 300 mg tablets, up to 600 mg three times daily
Other Names:
  • TRL PLA FCT.005
  • Film-coated tablet
  • Batch No.: X207 0802
  • Code: 3750411.005
  • Date of manufacture: September 2002
  • Date of evaluation: May 2004

Detailed Description:

This is an explorative controlled study with Oxcarbazepine (OXC) as an adjunct in the acute treatment of schizophrenia. The study will be performed in subjects between 18 and 50 years of age with an acute schizophrenic or schizophreniform disorder according to DSM-IV. The study will be performed according to Guidelines for Good Clinical Practice (GCP).

The primary hypothesis of this study is that adjunctive treatment with OXC yields at least comparable efficacy regarding antipsychotic actions with lower doses of neuroleptics and consequently substantially fewer adverse events.

A randomised controlled, double blind study is intended. During a 6 weeks treatment trial two groups of patients will be basically treated with olanzapine (starting with 5 mg after one week with an optional, BPRS-controlled step by step increase of about 2,5 mg each following week). Patients will receive a placebo controlled adjunctive therapy with OXC (1800 mg/day). After the initial lead-in of OXC within 7 days (allowing lorazepam as comedication), treatment with olanzapine will be started. Based on biometric calculations, a drop out adjusted sample size of 222 inpatients will be necessary

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical diagnosis of schizophrenia or schizophreniform psychosis according to DSM-IV
  • BPRS score > 36 and BPRS psychosis cluster > 12
  • Ability to provide written informed consent
  • Participants are required an adequate contraception

Exclusion Criteria:

  • Any severe neurological or somatic disorder
  • Other psychiatric disorders including addictive disorders
  • Positive urine drug screening for any compound except benzodiazepines
  • No pregnancy or breast feeding
  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: NCT00637234

Locations
Germany
Isar-Amper-Klinikum gemeinnützige GmbH, Klinik Taufkirchen (Vils)
Taufkirchen (Vils), Bayern, Germany, 84416
University of Cologne, Dept. of Psychiatry and Psychotherapy
Cologne, NRW, Germany, 50924
Sponsors and Collaborators
University of Cologne
Investigators
Study Director: F. Markus Leweke, MD University of Cologne
  More Information

Additional Information:
No publications provided

Responsible Party: Dr. F. Markus Leweke, University of Cologne
ClinicalTrials.gov Identifier: NCT00637234     History of Changes
Other Study ID Numbers: OXC-SCZ CTRI476BDE06
Study First Received: March 10, 2008
Last Updated: July 23, 2008
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Antipsychotic Agents
Carbamazepine
Oxcarbazepine
Analgesics
Analgesics, Non-Narcotic
Anticonvulsants
Antimanic Agents
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sensory System Agents
Sodium Channel Blockers
Therapeutic Uses
Tranquilizing Agents
Voltage-Gated Sodium Channel Blockers

ClinicalTrials.gov processed this record on October 29, 2014