Cardio Risk of Acute Schizophrenia Olanzapine Duke
Information source: Duke University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Schizophrenia; Schizoaffective Disorder
Intervention: Olanzapine (Drug); Metformin (Drug); Simvastatin (Drug)
Phase: Phase 4
Status: Withdrawn
Sponsored by: Duke University Official(s) and/or principal investigator(s): Joseph P McEvoy, MD, Principal Investigator, Affiliation: Duke University Medical Center, Dep't. Psychiatry
Summary
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
Clinical Details
Official title: Combined Treatment of Cardiovascular Risk Factors In Newly Admitted Patients With Schizophrenia or Schizoaffective Disorder Who Are Receiving Olanzapine And Matched Controls
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Prevention
Primary outcome: 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 outcome: 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.
Detailed description:
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
John Umstead Hospital, Butner, North Carolina 27509, United States
Duke University Medical Center, Durham, North Carolina 27705, United States
Additional Information
Starting date: April 2008
Last updated: July 29, 2014
|