Effects of Adjunctive Metformin on Metabolic Profiles in Clozapine-treated Schizophrenic Patients
Status:
Unknown status
Trial end date:
2011-07-01
Target enrollment:
Participant gender:
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.