Polypharmacy in Clozapine-resistant Schizophrenia (CLOZANS)

This study has been completed.
Sponsor:
Information provided by:
Niuvanniemi Hospital
ClinicalTrials.gov Identifier:
NCT00918021
First received: June 9, 2009
Last updated: November 18, 2010
Last verified: November 2010
  Purpose

The aim of this randomized, double-blind study is to verify the hypothesis that clozapine monotherapy is as efficient as a combination of clozapine and olanzapine therapy in treatment-resistant schizophrenia.

A third of schizophrenia patients are non -responders to medications used nowadays. These patients are usually treated with clozapine, but a large proportion of patients don't recover sufficiently. Therefore, these patients are treated with combination of two or more drugs to achieve better treatment results. Until now the scientific evidence has been insufficient to assess the utility of polypharmacy.

The aim is to study during 2009 with voluntary patients, if there is any benefit of olanzapine augmentation compared with pure clozapine monotherapy. During the study the patients are not exposed to any additional intervention. The intervention in this study is just to reduce the previously used polypharmacy.

Methods: This study lasts for 24 weeks. Participants (30) are randomized in one of two alternative interventions (A or B) before the study. After 12 weeks the intervention arms cross over (from A to B and from B to A).

Group B: In addition to clozapine, the participants receive their normal dosage of olanzapine (=the same as on the hospital ward) for 12 weeks, next the decreasing dosage of olanzapine for four weeks and subsequently placebo for 8 weeks

Group A: : In addition to clozapine the participants receive the decreasing dosage of olanzapine for four weeks, next placebo for 8 weeks, after that the increasing dosage of olanzapine for four weeks and subsequently the normal dosage of olanzapine for 8 weeks

The response for the medical treatment is assessed by Clinical Global Improvement Scale (CGIS) and Global Assessment of Functioning (GAF) -scale.

The primary outcomes are GAF and modified CGIS during the parallel phase of the study (the first 12 weeks). The second phase (the last 12 weeks) of the cross-over study is used in the secondary analysis. The use of additional medication (such as benzodiazepines) is used as a secondary outcome measure.


Condition Intervention Phase
Schizophrenia
Schizoaffective Disorder
Drug: olanzapine
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Olanzapine Augmentation in Clozapine-resistant Schizophrenia: a Randomized Double-blind Study

Resource links provided by NLM:


Further study details as provided by Niuvanniemi Hospital:

Primary Outcome Measures:
  • The primary outcomes are GAF and modified CGIS during the parallel phase of the study (the first 12 weeks). [ Time Frame: 0, 12, 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The second phase (the last 12 weeks) of the cross-over study is used in the secondary analysis. The use of additional medication (such as benzodiazepines) is used as a secondary outcome measure. [ Time Frame: 0, 12, 24 weeks ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: June 2009
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: olanzapine (B)
Group B: In addition to clozapine, the participants receive their normal dosage of olanzapine (=the same as on the hospital ward) for 12 weeks, next the decreasing dosage of olanzapine for four weeks and subsequently placebo for 8 weeks.
Drug: olanzapine
normal dosage of olanzapine (the same dosage as on hospital ward)
Other Name: Solazin
Placebo Comparator: placebo (A)
Group A: : In addition to clozapine the participants receive the decreasing dosage of olanzapine for four weeks, next placebo for 8 weeks, after that the increasing dosage of olanzapine for four weeks and subsequently the normal dosage of olanzapine for 8 weeks.
Drug: placebo
placebo

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age ≥18 years, (adult), legally competent
  • the patient is able to understand the purpose of the study and is eligible to sign the written informed consent form.
  • insufficient response to the valid clozapine-olanzapine -polypharmacy
  • psychotropic medication has been constant (unchangeable) during the past 2 months

Exclusion Criteria:

  • Pregnancy
  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: NCT00918021

Locations
Finland
Niuvanniemi Hospital
Kuopio, Finland, FI-70240
Sponsors and Collaborators
Niuvanniemi Hospital
Investigators
Principal Investigator: Jari Tiihonen, MD, PhD Niuvanniemi Hospital
  More Information

No publications provided

Responsible Party: Jari Tiihonen, Professor and Chairman, Niuvanniemi Hospital
ClinicalTrials.gov Identifier: NCT00918021     History of Changes
Other Study ID Numbers: 2009-011307-22, 0911885
Study First Received: June 9, 2009
Last Updated: November 18, 2010
Health Authority: Finland: Ethics Committee
Finland: Finnish Medicines Agency

Additional relevant MeSH terms:
Psychotic Disorders
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Clozapine
Olanzapine
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
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on July 22, 2014