Aggressive Treatment of Metabolic Syndrome in Patients Receiving Clozapine for Schizophrenia
Information source: North Shore Long Island Jewish Health System
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Metabolic Syndrome
Intervention: Pravastatin, Fenofibrate, Metformin, Orlistat, irbesartan (Drug); As selected by community physician (Other)
Status: Not yet recruiting
Sponsored by: North Shore Long Island Jewish Health System
Peter Manu, M.D., Phone: 718-470-8290, Email: firstname.lastname@example.org
Schizophrenia patients treated with clozapine have a high prevalence of obesity-related
metabolic syndrome. The condition is often poorly treated and may lead to the emergence of
coronary heart disease and type 2 diabetes. The study will investigate whether structured
treatment provided at the site of the outpatient psychiatric clinic of metabolic syndrome in
this populatio will decrease the severity of metabolic syndrome as compared with usual care
received by these patients in the community.
Official title: Aggressive Treatment of Metabolic Syndrome in Patients Treated With Clozapine for Schizophrenia
Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: Prevalence of metabolic syndrome
Compared with the general population, patients with schizophrenia have an increased risk of
death from atherosclerotic cardiovascular diseases (ASCVD) that reflect coronary heart
disease, stroke and peripheral vascular disease (Newcomer, 2007). Among the factors
contributing to the increased prevalence of ASCVD in schizophrenia are a) unhealthy
lifestyle (cigarette smoking, lack of physical activity, increased consumption of
calorie-dense foods rich in saturated fats and carbohydrates), b) genetic vulnerability to
glucose intolerance and diabetes; c) metabolic side-effects of psychotropic drugs; and d)
lack of access or compliance with community-based medical care, particularly clozapine or
olanzapine. Biologically, the common pathway leading to increased risk of ASCVD in
schizophrenia is the metabolic syndrome, an entity defined as 3 or more of the following 5
characteristics: abdominal obesity, increased blood pressure, increased fasting glucose,
increased levels of triglycerides and abnormally low levels of high-density lipoprotein
cholesterol. The prevalence of metabolic syndrome in schizophrenia ranges form 29% to 63%
and is significantly greater than the frequency of 21% in the general population (Correll et
al., 2006). As in the general population, the metabolic syndrome of patients with
schizophrenia is explained by increased intraabdominal adiposity leading to insulin
resistance and excess of circulating free fatty acids which are converted into
triglyceride-rich lipoproteins with atherogenic potential.
The treatment of metabolic syndrome relies primarily on therapeutic lifestyle changes aiming
to reduce weight, decrease intake of saturated fats and carbohydrates with high glycemic
index, eliminate smoking, and increase physical activity. Drug therapy is required for the
patients who fail to respond to lifestyle changes and the American Heart Association (AHA)
has published detailed guidelines for the pharmacologic management of metabolic syndrome
(Grundy et al., 2005). These guidelines are based on research indicating substantial
improvement in the risk of ASCVD of patients with metabolic syndrome treated with metformin
and acarbose for impaired glucose tolerance; statins, fibrates and nicotinic acid for lipid
abnormalities; angiotensin receptor blockers for increased blood pressure; and sibutramine
and orlistat for weight management. Some of these interventions (e. g., metformin and
sibutramine for weight management) have been completed in research settings with small
samples of patients with schizophrenia (Henderson et al., 2005; Wu et al., 2008) and have
produced promising results. However, treatment trials using the comprehensive AHA guidelines
have not yet been conducted in schizophrenics with metabolic syndrome.
Current Standard of Care at Zucker Hillside Hospital
The Aftercare Clinic at Zucker Hillside Hospital has the oldest Clozapine Clinic in the U. S.
Opened in 1987, the Clozapine Clinic has a current enrollment of 230 adult patients.
According to hospital policy, all Clozapine Clinic patients must have an annual physical
evaluation and laboratory tests for the detection of obesity, dyslipidemia, glucose
intolerance, hypertension and metabolic syndrome. The mandatory physical examinations are
performed by each patient's outside physician or by the Clinic's Nurse Practioners.
Laboratory testing is performed at Long Island Jewish Medical Center's laboratories. The
physical examinations and laboratory findings are reviewed by each patient's psychiatrists.
Patients with physical or laboratory abnormalities are referred for care to internal
medicine specialists (i. e., general internal medicine, endocrinology, cardiology) in private
practice or to the appropriate outpatient clinics at Long Island Jewish Medical Center as
deemed necessary by their psychiatrists. At the present time, it is not known how many
schizophrenia patients with metabolic syndrome treated in the Aftercare Program (outpatient
clinic) at ZHH receive care according to the standard defined by the American Heart
We plan to evaluate the effect of application of AHA guidelines for the treatment of
metabolic syndrome in patients with schizophrenia who are receiving clozapine, an
antipsychotic known to produce weight gain and metabolic abnormalities in a majority of
patients (Newcomer, 2006). The study will include only outpatients receiving care in the
Clozapine Clinic. .
The study's primary aim is to compare the effectiveness of managing metabolic syndrome in
schizophrenia at the site of psychiatric outpatient services (integrated care) with
treatment obtained and coordinated by the patients Hillside psychiatrist (usual care). We
propose that Integrated care will remove access barriers, improve compliance, enhance
communication between psychiatry and internal medicine providers, and facilitate education
for weight management and smoking cessation. The management of metabolic syndrome for
patients receiving integrated care will adhere to the AHA guidelines (Grundy et al., 2005)
which describe dietary, exercise and pharmacologic interventions that have been extensively
validated in the general population. All of the medications suggested in the guidelines have
been FDA-approved for the individual components of metabolic syndrome. The 'usual care'
group will receive the current standard of care set by Hillside Hospital.
Importance of the Study
This is the first randomized trial of a "no-barriers" model of medical care for an
underserved and vulnerable mentally ill population. To increase homogeneity of the study
population and significance of the expected difference between integrated and usual care,
the study will assess only patients with the same psychiatric diagnosis (schizophrenia),
treated with the same psychotropic (clozapine) in a single, well-established outpatient
setting. The duration of the study is adequate to demonstrate whether the metabolic syndrome
components respond to life style modification and /or specific pharmacological intervention.
Research Design and Methods
Integrated, on-site, medical management of metabolic syndrome in patients with schizophrenia
is superior to usual care in the community, primarily because it will remove barriers
related to access to medical providers and increase compliance with drug therapy and
laboratory testing. The improvement will lead to decreased frequency of metabolic syndrome
in the sample, decreased risk of future ASCVD events (as predicted by AHA-recommended
instruments), decreased waist circumference, fasting glucose, blood pressure and
triglyceride levels and increased levels of HDL.
Minimum age: 19 Years.
Maximum age: 79 Years.
- patients with schizophrenia treated with clozapine; age 19-79
- pregnant women, personal history of/or comorbid eating disorders
Locations and Contacts
Peter Manu, M.D., Phone: 718-470-8290, Email: email@example.com
Zucker Hillside Hospital, Glen Oaks, New York 11004, United States
Starting date: November 2008
Ending date: May 2010
Last updated: November 20, 2008