Effects of Adjunctive Metformin on Metabolic Profiles in Clozapine-treated Schizophrenic Patients

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2011 by Taipei Medical University WanFang Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
National Science Council, Taiwan
Information provided by:
Taipei Medical University WanFang Hospital
ClinicalTrials.gov Identifier:
NCT01300637
First received: February 17, 2011
Last updated: February 18, 2011
Last verified: February 2011
  Purpose

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.


Condition Intervention
Obesity
Metabolic Syndrome
Schizophrenia
Drug: Metformin
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Prevalence of Metabolic Syndrome and Effects of Adjunctive Metformin on Metabolic Profiles in Clozapine-treated Schizophrenic Patients

Resource links provided by NLM:


Further study details as provided by Taipei Medical University WanFang Hospital:

Primary Outcome Measures:
  • body weight change [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    We measure body weight before and after intervention, at week 2, 4, 8, 16, 24


Secondary Outcome Measures:
  • metabolic features [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    Our secondary outcomes included waist circumference, blood pressure, triglyceride, HDL-C, fasting glucose and insulin.


Estimated Enrollment: 60
Study Start Date: November 2008
Estimated Study Completion Date: July 2011
Estimated Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: metformin
metformin intervention group
Drug: Metformin
metformin 500 mg/pill; target dose 1500 mg/day for 24 weeks
Other Name: Diaformin 500 mg/pill
Placebo Comparator: placebo
placebo-controlled
Drug: placebo
identical-appearing pill of placebo
Other Name: Diaformin 500 mg/pill identical-appearing placebo

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   20 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01300637

Contacts
Contact: Chun-Hsin Chen, MD 886-2-29307930 ext 53961 chunhsin57@yahoo.com.tw
Contact: Mong-Liang Lu, MD 886-2-29307930 ext 53961 mongliang@hotmail.com

Locations
Taiwan
Taipei Medical University-WanFang Hospital Recruiting
Taipei, Taiwan, 116
Contact: Chun-Hsin Chen, MD    886-2-29307930 ext 53961    chunhsin57@yahoo.com.tw   
Contact: Mong-Liang Lu, MD    886-2-29307930 ext 53961    mongliang@hotmail.com   
Sponsors and Collaborators
Taipei Medical University WanFang Hospital
National Science Council, Taiwan
Investigators
Principal Investigator: Chun-Hsin Chen, MD Taipei Medical University-WanFang Hospital, Taipei, Taiwan
  More Information

No publications provided by Taipei Medical University WanFang Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Chun-Hsin Chen, Taipei Medical University-WanFang Hospital
ClinicalTrials.gov Identifier: NCT01300637     History of Changes
Other Study ID Numbers: 96064
Study First Received: February 17, 2011
Last Updated: February 18, 2011
Health Authority: Taiwan: Department of Health

Keywords provided by Taipei Medical University WanFang Hospital:
schizophrenia
clozapine
metabolic dysregulation
metformin

Additional relevant MeSH terms:
Metabolic Syndrome X
Schizophrenia
Syndrome
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Disease
Pathologic Processes
Metformin
Clozapine
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
GABA Antagonists
GABA Agents

ClinicalTrials.gov processed this record on September 16, 2014