Adjunctive Low-dose Metformin in Patients With Schizophrenia and Metabolic Abnormalities

NCT02751307 | Completed Phase 4 DMC

• 1 other identifier: TMU-JIRB 201303005
• Study Type: interventional
• Target: 55
• Locations: 0 countries
• Sites: N/A

Brief Summary

Metformin has been used for alleviating metabolic abnormalities in patients with schizophrenia. Until now, the lowest dose of metformin to treat metabolic abnormalities in clozapine-treated patients is 1000 mg/d. The aim of this study was to determine whether a lower dosage of metformin, such as 500 mg/d, is effective for improving metabolic profiles in clozapine-treated patients with pre-existing metabolic abnormalities. Methods: In this 12-week, randomized, double-blind, placebo-controlled trial, metformin 500 mg/d or 1000 mg/d or a placebo was prescribed to clozapine-treated patients with schizophrenia having pre-existing metabolic abnormalities. The recruited patients underwent physical and laboratory evaluations at week-4, week-8, and week-12.

Conditions

Metabolic Syndrome

Keywords

metformin; clozapine; schizophrenia; metabolic traits

Outcome Measures

Primary Outcomes (1)

• Changes in body weight

  baseline; week-4; week-8; week-12

Secondary Outcomes (6)

• Changes in waist circumference

  baseline; week-4; week-8; week-12

• Changes in blood pressure

  baseline; week-4; week-8; week-12

• Changes in fasting triglyceride level

  baseline; week-4; week-8; week-12

• Changes in fasting high-density lipoprotein cholesterol level

  baseline; week-4; week-8; week-12

• Changes in fasting glucose level

  baseline; week-4; week-8; week-12

Study Arms (3)

metformin 500 mg/d; clozapine 100 mg

ACTIVE COMPARATOR

In the first week, 500 mg of metformin was administered in the morning. In the second week, the dosage was revised to 500 mg of metformin in the morning and the placebo in the evening. During metformin intervention period, the clozapine dose remained unchanged in these recruited clozapine-treated patients.

Drug: metformin 500 mg; Drug: clozapine 100 mg

metformin 1000 mg/d; clozapine 100 mg

ACTIVE COMPARATOR

In the first week, 500 mg of metformin was administered in the morning. In the second week, 500 mg of metformin twice a day was administered. During metformin intervention period, the clozapine dose remained unchanged in these recruited clozapine-treated patients.

Drug: metformin 500 mg; Drug: clozapine 100 mg

placebo; clozapine 100 mg

PLACEBO COMPARATOR

In the first week, one pill of placebo was given and in the second week, placebo BID was given. During metformin intervention period, the clozapine dose remained unchanged in these recruited clozapine-treated patients.

Drug: metformin 500 mg; Drug: clozapine 100 mg

Interventions

metformin 500 mg DRUG

metformin 500 mg QAM for metformin 500 mg/d group; metformin 500 mg 1 BID for metformin 1000 mg/d

Also known as: Loditon

metformin 1000 mg/d; clozapine 100 mg; metformin 500 mg/d; clozapine 100 mg; placebo; clozapine 100 mg

clozapine 100 mg DRUG

Clozapine dose remained unchanged during metformin intervention period in recruited patients.

Also known as: Clozaril

metformin 1000 mg/d; clozapine 100 mg; metformin 500 mg/d; clozapine 100 mg; placebo; clozapine 100 mg

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• patients diagnosed with schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
• aged 20-65 years
• had taken clozapine for at least 3 months
• had at least one of the following metabolic abnormalities: BMI ≥ 24; WC \> 90 cm (men) or 80 cm (women); fasting serum TG level ≥ 150 mg/dL; fasting serum HDL-C level ≤ 40 mg/dL (men) or 50 mg/dL (women); systolic BP ≥ 130 or diastolic BP ≥ 85 mm Hg; current use of antihypertensive agents; and FPG level = 100-126 mg/dL.

You may not qualify if:

• history of diabetes mellitus
• current use of hypoglycemic or hypolipidemic agents
• pregnancy
• allergy to metformin
• a creatinine level \> 1.4 ng/dL
• an abnormal liver function test result
• chronic cardiopulmonary insufficiency.

Sponsors & Collaborators

• Taipei Medical University WanFang Hospital: lead
• Taipei City Hospital: collaborator

Related Publications (1)

• Chiu CC, Lu ML, Huang MC, Chen PY, Lin YK, Lin SK, Chen CH. Effects of Low Dose Metformin on Metabolic Traits in Clozapine-Treated Schizophrenia Patients: An Exploratory Twelve-Week Randomized, Double-Blind, Placebo-Controlled Study. PLoS One. 2016 Dec 14;11(12):e0168347. doi: 10.1371/journal.pone.0168347. eCollection 2016.

  PMID: 27973619 DERIVED

MeSH Terms

Conditions

Metabolic Syndrome; Schizophrenia

Interventions

Metformin; Clozapine

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Chun-Hsin Chen, MD

  Department of Psychiatry, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Psychiatrist

Study Record Dates

• First Submitted: April 19, 2016
• First Posted: April 26, 2016
• Study Start: May 1, 2013
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: April 28, 2016

Record last verified: 2016-04