NCT01300637

Brief 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
60

participants targeted

Target at P25-P50 for not_applicable obesity

Timeline
Completed

Started Nov 2008

Typical duration for not_applicable obesity

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2008

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2009

Completed
1.9 years until next milestone

First Submitted

Initial submission to the registry

February 17, 2011

Completed
4 days until next milestone

First Posted

Study publicly available on registry

February 21, 2011

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2011

Completed
Last Updated

February 21, 2011

Status Verified

February 1, 2011

Enrollment Period

5 months

First QC Date

February 17, 2011

Last Update Submit

February 18, 2011

Conditions

ObesityMetabolic SyndromeSchizophrenia

Keywords

schizophreniaclozapinemetabolic dysregulationmetformin

Outcome Measures

Primary Outcomes (1)

  • body weight change

    We measure body weight before and after intervention, at week 2, 4, 8, 16, 24

    24 weeks

Secondary Outcomes (1)

  • metabolic features

    24 weeks

Study Arms (2)

metformin

ACTIVE COMPARATOR

metformin intervention group

Drug: Metformin

placebo

PLACEBO COMPARATOR

placebo-controlled

Drug: placebo

Interventions

MetforminDRUG

metformin 500 mg/pill; target dose 1500 mg/day for 24 weeks

Also known as: Diaformin 500 mg/pill
metformin
placeboDRUG

identical-appearing pill of placebo

Also known as: Diaformin 500 mg/pill identical-appearing placebo
placebo

Eligibility Criteria

Age20 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • phase 1
  • fulfilled DSM-IV criteria of schizophrenia or schizoaffective disorder
  • 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).

You may not qualify if:

  • 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).
  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Taipei Medical University-WanFang Hospital

Taipei, 116, Taiwan

RECRUITING

Related Publications (1)

  • Chen CH, Huang MC, Kao CF, Lin SK, Kuo PH, Chiu CC, Lu ML. Effects of adjunctive metformin on metabolic traits in nondiabetic clozapine-treated patients with schizophrenia and the effect of metformin discontinuation on body weight: a 24-week, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2013 May;74(5):e424-30. doi: 10.4088/JCP.12m08186.

    PMID: 23759461DERIVED

MeSH Terms

Conditions

ObesityMetabolic SyndromeSchizophrenia

Interventions

Metformin

Condition Hierarchy (Ancestors)

OverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsInsulin ResistanceHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesSchizophrenia Spectrum and Other Psychotic DisordersMental Disorders

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic Chemicals

Study Officials

  • Chun-Hsin Chen, MD

    Taipei Medical University-WanFang Hospital, Taipei, Taiwan

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Chun-Hsin Chen, MD

CONTACT

886-2-29307930chunhsin57@yahoo.com.tw

Mong-Liang Lu, MD

CONTACT

886-2-29307930mongliang@hotmail.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

February 17, 2011

First Posted

February 21, 2011

Study Start

November 1, 2008

Primary Completion

April 1, 2009

Study Completion

July 1, 2011

Last Updated

February 21, 2011

Record last verified: 2011-02

Locations

TW(1)