Topiramate vs Metformin on Cardio-Metabolic Profile in Schizophrenia on Atypical Antipsychotics

August 21, 2023 updated by: BISWA RANJAN MISHRA, All India Institute of Medical Sciences, Bhubaneswar

Efficacy and Safety of Add-on Topiramate vs Metformin on Cardio-Metabolic Profile in Patients With Schizophrenia on Atypical Antipsychotics With Metabolic Syndrome: a Randomized Controlled Trial

Metabolic syndrome is common in patients of schizophrenia. It can add to morbidity, loss of functionality and discontinuation of antipsychotic medication. Apart from metformin, there are limited treatment options as add on-s to antipsychotics for treatment of metabolic syndrome. There have been placebo-controlled studies of Topiramate as an adjuvant but the present study would be the first head-on trial between these drugs for treatment of metabolic syndrome in patients of schizophrenia.

If the outcome measures show a significant improvement with add on topiramate when compared with Metformin, then add on Topiramate can be a preferred treatment for metabolic syndrome in patients with schizophrenia on atypical antipsychotics. The adverse effects of Metformin can be side-stepped and Topiramate can also be given in conditions which are contraindications for Metformin. Thus, Topiramate can be a good alternative to metformin especially in conditions like liver, cardiac and renal impairment where metformin use should be avoided. Topiramate can not only improve metabolic parameters but can also have a beneficial effect on the symptom severity of schizophrenia. Thus, it can be a good augmentation drug to be used along with antipsychotics in these patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study Design: The proposed study will be a randomised, parallel arm, active controlled, open label, clinical trial.

Study Setting: The proposed study will be conducted at the out-patient (OP) and the in-patient (IP) settings of the Department of Psychiatry, All India Institute of Medical Sciences, Bhubaneswar.

Study Groups: The study population will comprise of 60 patients with schizophrenia (F20 according to ICD 10 DCR) on atypical antipsychotics for more than 3 months diagnosed with metabolic syndrome.

Sample size: Sample size calculation has been done based on the expected difference in the cardiovascular risk scoring (QRISK3), the primary outcome measure of our study. Sample size of 23 per group will achieve a power of 80%, to detect the difference of 5% in cardiovascular risk scoring (QRISK3) between the groups with standard deviation as 6.0 and a level of significance 0.05. Assuming an attrition rate of 25%, 30 patients will be recruited per group.

Details of Control(s): It is an active controlled study where the control group will receive add-on metformin along with the ongoing atypical antipsychotic.

Details of intervention:

The patients who are randomized to Topiramate group will be receiving Topiramate at a stable dose of 50 mg/day during the study period that is for 8 weeks along with the ongoing atypical antipsychotic.

The patients who are randomized to Metformin group will be receiving Metformin at dose of 500 mg/day twice a day, a total of 1000 mg/day for 8 weeks along with the ongoing atypical antipsychotic.

Duration of study: The study will be conducted for a period of 18 months

Investigation specifically related to Protocols:

The following Psychiatric scales will be used:

  1. PANSS: The Positive and Negative Syndrome Scale
  2. CGI-SCH Scales: The Clinical Global Impression-Schizophrenia scale (for Severity and Improvement) The following investigations will be done for cardio-metabolic profile;

a) QRISK3 b) Lipid profile c)Fasting serum insulin by ELISA for insulin resistance (HOMA-IR) d)Fasting blood glucose for insulin resistance (HOMA-IR)

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Odisha
      • Bhubaneswar, Odisha, India, 751019
        • Dept of Psychiatry, Aiims, Bhubaneswar

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients clinically diagnosed with schizophrenia (F20 according to ICD-10 DCR) on a stable dose of atypical antipsychotic for more than 3 months.
  • Patients with metabolic syndrome (as per NCEP ATP III Definition).
  • Patients above 25 years of age of either gender.
  • Legally authorized representative (LAR) giving voluntary written consent for participation in the study.

Exclusion Criteria:

  • Patients on combination of antipsychotics.
  • Patients having any contraindication for Metformin/Topiramate.
  • History of any psychoactive substance use in harmful use or dependence pattern except tobacco.
  • Any co-morbid medical, psychiatric or neurological disorders like hypertension, coronary artery disease, hypothyroidism, arthritis.
  • History of any significant head injury or organic diseases.
  • Pregnant and breastfeeding females.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Metformin arm
1000mg for 8 weeks
Drug: Metformin
1000mg for 8 weeks
Other Names:
  • Dibeta SR
  • Metgen
  • Glycomet
Experimental: Topiramate arm
50mg for 8 weeks
Drug: Topiramate
50mg for 8 weeks
Other Names:
  • Topamax
  • Topirol
  • Topaz

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the QRISK3 score.
Time Frame: 8 weeks
QRISK3 (QRESEARCH cardiovascular risk algorithm)2018 algorithm- used for calculating the cardiovascular risk in the upcoming 10 years. It is measured for the age group of 25 to 84 years using information like age, weight, height, BMI, Lipid profile, past history of CKD, angina, migraine etc. Higher score indicates higher risk.
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the LDL/HDL ratio(Low density lipoprotein/High density lipoprotein).Higher ratio indicates higher risk
Time Frame: 8 weeks
Calculated from the lipid profile
8 weeks
Change in Insulin Resistance (HOMA-IR)(homeostasis model assessment-estimated insulin resistance ).
Time Frame: 8 weeks
Calculated from serum insulin level and fasting glucose level according to the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
8 weeks
Change in Positive and negative syndrome scale
Time Frame: 8 weeks
Positive and negative syndrome scale, a scale used to measure the symptom severity in patients of schizophrenia including positive, negative and general psychopathology.Higher scores indicate more severity of illness.Maximum score 30 and maximum 210
8 weeks
Change in Clinical Global Impression-Schizophrenia scale
Time Frame: 8 weeks
Scale that is used to measure the baseline severity, change in severity of illness with treatment and global improvement. More score indicates more impairment.
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

All India Institute of Medical Sciences, Bhubaneswar

Investigators

  • Principal Investigator: Biswa Ranjan Mishra, MD, DPM, All India Institute of Medical Sciences, Bhubaneswar

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 20, 2022

Primary Completion (Actual)

July 30, 2023

Study Completion (Actual)

August 20, 2023

Study Registration Dates

First Submitted

December 4, 2021

First Submitted That Met QC Criteria

December 15, 2022

First Posted (Actual)

December 23, 2022

Study Record Updates

Last Update Posted (Actual)

August 22, 2023

Last Update Submitted That Met QC Criteria

August 21, 2023

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AIIMS BBSR/PG Thesis/2021-22

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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