Effects of Adjunctive Metformin on Metabolic Profiles in Clozapine-treated Schizophrenic Patients
Information source: Taipei Medical University WanFang Hospital
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Obesity; Metabolic Syndrome; Schizophrenia
Intervention: Metformin (Drug); placebo (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: Taipei Medical University WanFang Hospital Official(s) and/or principal investigator(s): Chun-Hsin Chen, MD, Principal Investigator, Affiliation: Taipei Medical University-WanFang Hospital, Taipei, Taiwan
Overall contact: Chun-Hsin Chen, MD, Phone: 886-2-29307930, Ext: 53961, Email: chunhsin57@yahoo.com.tw
Summary
Background: Several studies have suggested that clozapine has the greatest propensity of all
available atypical antipsychotics to induce weight gain and metabolic dysregulation. So it
is necessary to conduct some interventions to prevent or treat metabolic dysregulation
induced by clozapine.
Metformin has been reported to achieve weight loss in several groups of patients
characterized by insulin resistance. Several studies evaluated the effects of metformin on
antipsychotics-induced weight gain and study period lasted from 8 to 16 weeks. Long-term
metformin use had more robust effect on metabolic dysregulation and body weight in
non-psychiatric field.
Goals: The study goals are two-fold. The first goal is to estimate the prevalence of
metabolic dysregulation among clozapine-treated schizophrenic patients in Taiwan. The second
goal is to assess the reversal effect of metformin on metabolic disturbance among
clozapine-treated schizophrenic patients in a 24-week double-blind, placebo-control trial.
The investigators will use metformin 1500 mg/d or placebo in the second phase trial.
Methods: This study will be divided into two phases. The first phase is to estimate the
prevalence of metabolic disturbances among clozapine-treated patients. The second will be a
randomized, double-blind, and placebo-controlled study of adjunctive metformin for non-DM
clozapine-treated patients.
The clozapine dosage was maintained unchanged during the study period. The eligible patients
will be randomly assigned to either metformin or identical placebo pills. Metformin will be
titrated to 1500 mg/day in 4 weeks. Patients' blood pressure (BP), waist circumference, body
weight, fasting plasma glucose (FPG), triglyceride (TG), high-density lipoprotein
cholesterol (HDL), insulin, and leptin will be measured at 2, 4, 8, 16, and 24 weeks after
the start of metformin.
In a 3-year period, the investigators estimate to recruit 150 clozapine-treated patients in
the first phase and 75 fulfill the second phase criteria. The investigators estimate 60
patients complete the second phase intervention (staying in second phase at least 4 weeks).
From this study, the investigators would like to know the prevalence of metabolic
dysregulation among clozapine-treated schizophrenic patients and to know the effect of
metformin on metabolic profile among non-DM clozapine treated patients.
Clinical Details
Official title: Prevalence of Metabolic Syndrome and Effects of Adjunctive Metformin on Metabolic Profiles in Clozapine-treated Schizophrenic Patients
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: body weight change
Secondary outcome: metabolic features
Detailed description:
Background: Several studies have suggested that clozapine has the greatest propensity of all
available atypical antipsychotics to induce weight gain and metabolic dysregulation. So it
is necessary to conduct some interventions to prevent or treat metabolic dysregulation
induced by clozapine.
Metformin has been reported to achieve weight loss in several groups of patients
characterized by insulin resistance. Several studies evaluated the effects of metformin on
antipsychotics-induced weight gain and study period lasted from 8 to 16 weeks. Long-term
metformin use had more robust effect on metabolic dysregulation and body weight in
non-psychiatric field. In our recent study data showed that after 8 weeks treatment with
metformin 1500 mg/day in 24 olanzapine-treated patients, the body weight, fasting levels of
glucose, triglyceride, and insulin significantly decreased. Insulin secretion and insulin
resistance also decreased significantly. Half of subjects with metabolic syndrome obtained
improvement after metformin trial.
Goals: The study goals are two-fold. The first goal is to estimate the prevalence of
metabolic dysregulation among clozapine-treated schizophrenic patients in Taiwan. The second
goal is to assess the reversal effect of metformin on metabolic disturbance among
clozapine-treated schizophrenic patients in a 24-week double-blind, placebo-control trial.
We will use metformin 1500 mg/d or placebo in the second phase trial.
Methods: This study will be divided into two phases. The first phase is to estimate the
prevalence of metabolic disturbances among clozapine-treated patients. The second will be a
randomized, double-blind, and placebo-controlled study of adjunctive metformin for non-DM
clozapine-treated patients.
Patients are recruited in the first phase if they meet the following criteria (1) fulfilled
DSM-IV criteria of schizophrenia or schizoaffective disorder; (2) 18-65 year of age (3)
receiving clozapine for at least 6 months. We will check patients' blood pressure (BP),
waist circumference, body weight, fasting plasma glucose (FPG), triglyceride (TG),
high-density lipoprotein cholesterol (HDL), insulin, and leptin will be measured. In this
study, we use the modified ATP III criteria for Asians to evaluate subjects for a diagnosis
of metabolic syndrome.
The inclusion criteria of second phase intervention will be first-phase participants who are
(1) overweight and obese (BMI ≧ 24) or (2) one or more metabolic dysregulation, such as
abdominal obesity (waist circumference > 90 cm, in men and > 80 cm, in women; fasting
hypertriglyceridemia, (≥ 150 mg/dL); low fasting HDL levels (< 40 mg/dL in men and < 50
mg/dL in women); high blood pressure (≥ 130/ ≥ 85 mm Hg or current treatment with
antihypertensive medication). The exclusion criteria are the following: (1) current use of
hypoglycemic or hypolipidemic agents (2) FPG levels ≥ 126 mg/dL; (3) women who are pregnant;
(4) known allergy or contraindicated to metformin (including Creatine>1. 4 ng/dl; abnormal
liver function test; chronic cardiopulmonary insufficiency).
The clozapine dosage was maintained unchanged during the study period. The eligible patients
will be randomly assigned to either metformin or identical placebo pills. Metformin will be
titrated to 1500 mg/day in 4 weeks. Patients' blood pressure (BP), waist circumference, body
weight, fasting plasma glucose (FPG), triglyceride (TG), high-density lipoprotein
cholesterol (HDL), insulin, and leptin will be measured at 2, 4, 8, 16, and 24 weeks after
the start of metformin.
In a 3-year period, we estimate to recruit 150 clozapine-treated patients in the first phase
and 75 fulfill the second phase criteria. We estimate 60 patients complete the second phase
intervention (staying in second phase at least 4 weeks).
From this study, we would like to know the prevalence of metabolic dysregulation among
clozapine-treated schizophrenic patients and to know the effect of metformin on metabolic
profile among non-DM clozapine treated patients.
Key words: schizophrenia, clozapine, metabolic dysregulation, metformin
Eligibility
Minimum age: 20 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
phase 1
- fulfilled DSM-IV criteria of schizophrenia or schizoaffective disorder
- 18-65 year of age
- receiving clozapine for at least 6 months.
phase 2 are those in phase 1 and met the following
- overweight and obese (BMI ≧ 24)
- one or more metabolic dysregulation, such as abdominal obesity (waist circumference >
90 cm, in men and > 80 cm, in women
- fasting hypertriglyceridemia, (≥ 150 mg/dL)
- low fasting HDL levels (< 40 mg/dL in men and < 50 mg/dL in women)
- high blood pressure (≥ 130/ ≥ 85 mm Hg or current treatment with antihypertensive
medication).
The exclusion criteria are the following:
- current use of hypoglycemic or hypolipidemic agents
- FPG levels ≥ 126 mg/dL
- women who are pregnant
- known allergy or contraindicated to metformin (including Creatine>1. 4 ng/dl abnormal
liver function test; chronic cardiopulmonary insufficiency).
Exclusion Criteria:
phase 2
- current use of hypoglycemic or hypolipidemic agents
- FPG levels ≥ 126 mg/dL
- women who are pregnant
- known allergy or contraindicated to metformin (including Creatine>1. 4 ng/dl abnormal
liver function test
- chronic cardiopulmonary insufficiency).
Locations and Contacts
Chun-Hsin Chen, MD, Phone: 886-2-29307930, Ext: 53961, Email: chunhsin57@yahoo.com.tw
Taipei Medical University-WanFang Hospital, Taipei 116, Taiwan; Recruiting Chun-Hsin Chen, MD, Phone: 886-2-29307930, Ext: 53961, Email: chunhsin57@yahoo.com.tw Mong-Liang Lu, MD, Phone: 886-2-29307930, Ext: 53961, Email: mongliang@hotmail.com
Additional Information
Starting date: November 2008
Last updated: February 18, 2011
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