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

Sponsor

All India Institute of Medical Sciences, Bhubaneswar (Other)

Overall Status

Recruiting

CT.gov ID

NCT05663749

Collaborator

(none)

Enrollment

Location

Arms

10.3

Anticipated Duration (Months)

5.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Metabolic Syndrome Schizophrenia	Drug: Metformin Drug: Topiramate	Phase 4

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:

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

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 Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 20, 2022

Anticipated Primary Completion Date :

May 30, 2023

Anticipated Study Completion Date :

Jul 30, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change in the QRISK3 score. [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.

Secondary Outcome Measures

Change in the LDL/HDL ratio(Low density lipoprotein/High density lipoprotein).Higher ratio indicates higher risk [8 weeks]
Calculated from the lipid profile
Change in Insulin Resistance (HOMA-IR)(homeostasis model assessment-estimated insulin resistance ). [8 weeks]
Calculated from serum insulin level and fasting glucose level according to the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
Change in Positive and negative syndrome scale [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
Change in Clinical Global Impression-Schizophrenia scale [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.