- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00672464
Cardio Risk of Acute Schizophrenia Olanzapine Duke (CRASOD)
Combined Treatment of Cardiovascular Risk Factors In Newly Admitted Patients With Schizophrenia or Schizoaffective Disorder Who Are Receiving Olanzapine And Matched Controls
Primary Objective: To compare added metformin and/or added simvastatin versus no intervention in reducing or eliminating increased cardiovascular risk (as estimated by elevation in non-HDL cholesterol levels) during the treatment of schizophrenia with olanzapine.
Secondary Objective(s): To compare added metformin and/or added simvastatin versus no intervention in reducing or eliminating increased cardiovascular risk (as estimated by elevation in triglyceride levels) during the treatment of schizophrenia with olanzapine. To compare added metformin and/or added simvastatin versus no intervention in reducing or eliminating increased cardiovascular risk (as estimated by C-reactive protein levels) during the treatment of schizophrenia with olanzapine
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
Olanzapine offers greater therapeutic antipsychotic benefit than the other non-clozapine antipsychotic medications available in the U.S., making it a desirable choice for the long-term maintenance treatment of patients with schizophrenia (Lieberman et al, 2005). Long-term compliance with an efficacious antipsychotic medication is fundamental to optimal therapeutic outcomes. Toward this goal, a long-acting injectable preparation of olanzapine will soon be available.
However, the long-term use of olanzapine has been limited by its substantial, un-wanted effects on metabolism that result in weight gain, increases in insulin resistance, increases in non-HDL-cholesterol, and increases in C-reactive protein (Lieberman et al, 2005; McEvoy et al, 2005;Meyer et al, 2008; McEvoy et al, in submission). Over the long term, insulin resistance contributes to the accelerated incidence of diabetes mellitus that has been observed among patients with schizophrenia since the availability of the atypical antipsychotic medication (Basu A, 2006). Over the long term, elevated non-HDL-cholesterol and increased inflammation contribute independently to the accelerated cardiovascular mortality that has been observed among patients with schizophrenia since the availability of the atypical antipsychotic medications (Saha et al, 2007, Capasso et al, 2007). Inflammation, as measured by C-reactive protein, provides added, independent predictive value of cardiovascular risk beyond that of measures of insulin resistance and elevated non-HDL-cholesterol.
Established strategies exist that may attenuate these unwanted effects of olanzapine on metabolism and inflammation. Metformin has been shown to reduce weight gain and insulin resistance in pre-diabetic, obese individuals without mental problems (Salpeper et al, 2008) and in patients treated with atypical antipsychotic medications (Wu et al, 2008). Statins have been shown to reduce non-HDL-cholesterol and cardiovascular morbidity and mortality (Lee et al, 2007). Both metformin and statins have been shown to reduce C-reactive protein (Bulcau et al, 2007).
We propose to implement a pilot study to estimate the effects sizes (for change in triglycerides, change in non-HDL-cholesterol, and change in CRP) of added metformin, added simvastatin, or added metformin and simvastatin, versus added no intervention in 120 newly-admitted, acutely psychotic, recently un-medicated patients with schizophrenia over 4 weeks of prospective treatment with olanzapine. We will also compare these patients (baseline values, in the not recently medicated state) to 40 age, race, and gender matched control subjects on fasting triglycerides, non-HDL-cholesterol, and CRP levels.
We will recruit newly admitted patients experiencing an acute psychotic relapse of schizophrenia (related to failure to take their prescribed antipsychotic medication). After baseline assessments and samplings have been completed, all patient will be treated with olanzapine zydis 15 mg QHS for 28 days. All patients will be randomized 1:1:1:1 to added metformin, added simvastatin, added metformin and simvastatin, or no intervention. All treatments will be open label. Repeated assessments of weight, non-HDL-cholesterol, triglycerides and C-reactive protein will be obtained. Subjects will remain as inpatients at JUH for the duration of the study.
Studietype
Fase
- Fase 4
Kontakter og plasseringer
Studiesteder
-
-
North Carolina
-
Butner, North Carolina, Forente stater, 27509
- John Umstead Hospital
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Durham, North Carolina, Forente stater, 27705
- Duke University Medical Center
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
- We will include patients who come to us free of antipsychotic medication, i.e., patients with chronic schizophrenia (with at least one prior psychiatric hospitalization) who have been off antipsychotic medication for at least 3 weeks and who are newly hospitalized for treatment of an acute psychotic relapse; these patients will be male or female, 18-60 years of age, meet DSM-IV criteria for schizophrenia, and have scores >=4 on at least two of the PANSS Positive subscale items.
Exclusion Criteria:
- We will exclude patients whose psychoses are predominantly affective in nature or explainable on the basis of substance abuse or a co-morbid medical condition, patients with diabetes mellitus, epilepsy, mental retardation, or organic mental syndromes, and patients currently taking metformin or a statin.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Forebygging
- Tildeling: Randomisert
- Intervensjonsmodell: Faktoriell oppgave
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
---|---|
Aktiv komparator: Olanzapine only
Newly Admitted Patients with Schizophrenia or Schizoaffective Disorder Who Are Receiving Olanzapine
|
Olanzapine zydis 15 mg QHS for 28 days
|
Eksperimentell: Added Metformin
Newly Admitted Patients with Schizophrenia or Schizoaffective Disorder Who Are Receiving Olanzapine with Added Metformin
|
Olanzapine zydis 15 mg QHS for 28 days
Metformin capsules will be started at 500 mg twice a day (before breakfast and before dinner) for days 1-3, then 500 mg before breakfast and 1000 mg before dinner for days 4-7, and then 1000 mg twice a day thereafter.
|
Eksperimentell: Added Simvastatin
Newly Admitted Patients with Schizophrenia or Schizoaffective Disorder Who Are Receiving Olanzapine with Added Simvastatin
|
Olanzapine zydis 15 mg QHS for 28 days
Simvastatin will be started at 10 mg at bed time for the first week and 20 mg at bedtime thereafter.
|
Eksperimentell: Added Metf. + Simv.
Newly Admitted Patients with Schizophrenia or Schizoaffective Disorder Who Are Receiving Olanzapine with Added Metformin and Simvastatin
|
Olanzapine zydis 15 mg QHS for 28 days
Metformin capsules will be started at 500 mg twice a day (before breakfast and before dinner) for days 1-3, then 500 mg before breakfast and 1000 mg before dinner for days 4-7, and then 1000 mg twice a day thereafter.
Simvastatin will be started at 10 mg at bed time for the first week and 20 mg at bedtime thereafter.
|
Ingen inngripen: Matched Controls
Matched Control Subjects by age, race, and gender
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
---|---|
To compare added metformin and/or added simvastatin versus no intervention in reducing or eliminating increased cardiovascular risk (as estimated by elevation in non-HDL cholesterol levels) during the treatment of schizophrenia with olanzapine.
Tidsramme: 28 days
|
28 days
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
---|---|
To compare added metformin and/or added simvastatin versus no intervention in reducing or eliminating increased cardiovascular risk during the treatment of schizophrenia with olanzapine.
Tidsramme: 28 days
|
28 days
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Joseph P McEvoy, MD, Duke University Medical Center, Dep't. Psychiatry
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Forventet)
Studiet fullført (Forventet)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Psykiske lidelser
- Schizofrenispektrum og andre psykotiske lidelser
- Schizofreni
- Psykotiske lidelser
- Hypoglykemiske midler
- Fysiologiske effekter av legemidler
- Nevrotransmittere agenter
- Molekylære mekanismer for farmakologisk virkning
- Sentralnervesystemdepressiva
- Autonome agenter
- Agenter fra det perifere nervesystemet
- Enzymhemmere
- Antimetabolitter
- Antiemetika
- Gastrointestinale midler
- Antikolesteremiske midler
- Hypolipidemiske midler
- Lipidregulerende midler
- Hydroksymetylglutaryl-CoA-reduktasehemmere
- Antipsykotiske midler
- Beroligende midler
- Psykotropiske stoffer
- Serotoninopptakshemmere
- Nevrotransmitter opptakshemmere
- Membrantransportmodulatorer
- Serotoninmidler
- Olanzapin
- Metformin
- Simvastatin
Andre studie-ID-numre
- Pro00006916
- None (investigator sponsored)
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