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van CCT (UK)

van CCT (UK)

Effect of clozapine and olanzapine on the use of drugs and alcohol by patients with schizophrenia and related disorders

- candidate number3172
- NTR NumberNTR1267
- ISRCTNISRCTN wordt niet meer aangevraagd
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR3-apr-2008
- Secondary IDs637 ZonMW
- Public TitleEffect of clozapine and olanzapine on the use of drugs and alcohol by patients with schizophrenia and related disorders
- Scientific TitleClozapine vs olanzapine as second generation antipsychotic medication (SGA) in the six months treatment of patients with schizophrenia and related disorders and co-morbid substance use disorders (SUD): a multi-centre double blind randomized trial
- ACRONYMRandomized Olanzapine Clozapine Key study Schizophrenia Addiction Netherlands [ROCKSAN]
- hypothesisPrimary research question: Is there a difference in effectiveness and costs of clozapine treatment compared to olanzapine treatment in the reduction of substance use disorders of patients with schizophrenia and related psychotic disorders?
Secondary research question: Are there differences in effectiveness and costs of clozapine treatment compared to olanzapine treatment in: psychopathology, adverse effects, compliance, drop out rate, psychosocial functioning and quality of life?
- Healt Condition(s) or Problem(s) studiedSchizophrenia, Olanzapine, Substance abuse, Clozapine, Randomized Controlled Trial (RCT), Double blind
- Inclusion criteria1. Diagnosis of schizophrenia or schizoaffective disorder or schizophreniform disorder according to DSM-IV with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (SCID-P)
2. Diagnosis of Substance Use Disorder according to DSM IV
3. Age between 18-50 years (extremes included)
4. Patients should be able to understand the study description and give informed consent after detailed information
- Exclusion criteriaDetailed exclusion criteria
1. Pregnancy
2. Lactating women
3. Female subject without adequate contraception
4. Known hypersensitivity to any ingredient of clozapine or olanzapine
5. Concomitant use of any other antipsychotic drug than clozapine or olanzapine
6. Preferred use of other psychotropic medication other than oxazepam or biperideen
7. Narrow-angle glaucoma
8. Known neurological or endocrine disease
9. Myeloproliferative disorder
10. Uncontrolled epilepsy
11. History of clozapine-induced severe granulocytopenia
12. Paralytic ileus
- mec approval receivedno
- multicenter trialyes
- randomisedyes
- masking/blindingDouble
- controlActive
- groupParallel
- Type2 or more arms, randomized
- Studytypeintervention
- planned startdate 1-okt-2008
- planned closingdate1-okt-2011
- Target number of participants140
- InterventionsRCT: olanzapine or clozapine. In the first period the study drug dose is titrated over 4 weeks according to a fixed dose schedule (see attached scheme). All patients in both treatment arms will receive additional standard treatment and care. Treatment failure or medication switch during will be a secondary endpoint. At baseline, week 4, week 8 and month 6 or at drop out from study we will assess:
- Primary outcomePrimary efficacy measures:
at baseline, week 4, week 8, month 6 and at moment of unblinding:
Self reported drug use
- CIDI SAM: self-report substance use
- Recent Drug Use Urinalysis (RDUU): a laboratory semiquantitative test on the presence of cannabis, heroin,cocaine and amphetamines (including XTC)
- Secondary outcomePsychopathology:
- Positive and negative symptoms: Positive And Negative Syndrome Scale (PANSS) (Kay et al., 1989) based on Information collected in a semi-structured interview (SCI-PANSS)
- (Re) admission in psychiatric and course of symptoms in psychiatric hospital during 6 months as measured with the LCS (Susser et al, 2000) at baseline and at month 6
- Y-BOCS at baseline and at month 6 Adverse effects:- leukopenia, agranulocytosis (clozapine), weekly blood count during 16 week than monthly - weight gain
- ESRS: Extra pyramidal Symptom Rating Scale (Chouinard)
- Time to non- compliance as assessed by the central as assessed with the Treatment Compliance Interview, Patient and Clinicians Version (Weiden et al.)
- Drop-out
Quality of life/utility:
- EuroQol 5-D questionnaire: In the EQ-5D approach,health related quality of life is conceptualized as having physical, mental, and social domains. The patients will be asked to classify themselves on five dimensions of health, each with three levels of dysfunction: mobility, self-care, usual activities, discomfort, and anxiety/depression.
- Global Assessment of functioning (GAF) scale
- Quality adjusted life years (QALYs).
To this end, data on survival and quality of life (utility scores at baseline and 6 months weeks), measured by the the EQ-5D will be collected
- Costs associated with schizophrenia and SUD’s (S+SUD) from a societal perspective, this includes direct and indirect medical costs, and non-medical costs:
1. Direct S+SUD related health care costs: will be collected from a treatment inventory, pharmacy records (will be collected retrospectively) and information from the specialist.
2. Direct non-medical costs: cost for travelling.
3. lndirect non-medical costs (costs due to productivity losses) Health and Labor Questionnaire: self-administered instrument with proven ability to measure absence from work, reduced productivity at paid work, unpaid labour production and impediments to paid and unpaid labour
- lncremental cost-effectiveness ratio (ICER): the difference in effectiveness (clozapine-other SGA’s)/ difference in costs
- Timepointsbaseline, month 1, month 2, month 6 and at drop out
- Trial web siteN/A
- statusplanned
- Sponsor/Initiator Academic Medical Center (AMC), Amsterdam
- Funding
(Source(s) of Monetary or Material Support)
ZON-MW, The Netherlands Organization for Health Research and Development
- Publications
- Brief summaryThe lifetime prevalence of alcohol- and substance use disorders of patients with schizophrenia varies from 40% to 70%.Substances commonly abused by patients with schizophrenia include nicotine, alcohol and drugs, such as cannabis, cocaine and amphetamines. Studies of patients with schizophrenia have clearly indicated that co-morbid substance abuse is associated with overall poorer outcome of schizophrenia. Recent correlational studies suggest that clozapine has a favourable effect on substance abuse and dependence in schizophrenia. This possible benefit should be weighted against the risk of adverse effects. However, evidence to include clozapine in treatment recommendations in patients with schizophrenia or related disorders and substance use disorders is missing. Therefore we propose to conduct a double blind randomized clinical trial comparing the effects of clozapine with olanzapine on the severity of substance use based on urine analysis and self report. Secondary outcome measures will include hospitalization, improvement of psychosis and negative symptoms, relapse of florid psychosis, side effects, non-compliance, drop-out rate, psychosocial functioning and quality of life. Direct and indirect medical and non-medical costs of treatment with clozapine compared with olanzapine will be evaluated. The direct treatment costs of clozapine are estimated to be higher than those of treatment with other atypical antipsychotic medications. However, we expect that clozapine treatment will also decrease substance abuse and dependence outcomes and reduce associated resource utilization (direct medical and non-medical costs) more than olanzapine. Participants of the study will be in- and outpatients age 18 to 50, meeting DSM-IV criteria for schizophrenia, schizoaffective or schizophreniform disorder and substance use disorders. Eligible patients will be recruited from in-and outpatient settings of the Academic Medical Centre (Amsterdam) and several mental health services. In a double blind randomized controlled trial patients will be randomized to receive clozapine or olanzapine. The total sample size of the study will be 120 patients. With an estimated attrition rate of 15% this will lead to a total study sample of 140 patients.
- Main changes (audit trail)
- RECORD3-apr-2008 - 14-apr-2008

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