Metformin Treatment on Cognitive Impairment of Schizophrenia Co-morbid Metabolic Syndrome

Study Overview
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Brief Summary
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In this study, the investigators will investigate the impact and the related mechanism of metformin treatment on cognitive impairment of schizophrenia with a high risk of metabolic syndrome. Patients will be randomized to the metformin group or non-metformin control group (40 patients per arm) for 24 weeks. Clinical assessment will be done at screen/baseline, 4 weeks, 12 weeks, and 24 weeks. The specific aims are to compare the metformin group versus controls on 1) clinical core symptoms; 2) cognition. Biological samples also will be collected, and stored to research related mechanisms.

Detailed Description
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In this study, the investigators will investigate the impact and the related mechanism of metformin treatment on cognitive impairment of schizophrenia with a high risk of metabolic syndrome. Patients will be randomized to the metformin group or non-metformin control group (40 patients per arm) . Clinical assessment will be done at screen/baseline, 4 week, 12 week and 24 week. The specific aims are to compare the metformin group versus controls on: 1) clinical core symptoms; 2) cognition. Biological samples also will be collected, and stored to research related mechanisms. Clinical symptoms will be measured by the Positive and Negative Syndrome Scale and Calgary Depression Scale for Schizophrenia (Chinese version). Cognitive function will be assessed by the MATRICS Consensus Cognitive Battery. The investigators hypothesize that 1) metformin may improve the cognitive impairment of schizophrenia patients; 2) metformin may alter oxidative stress indexes or inflammatory biomarkers thus influencing the oxidative and inflammatory mechanism, and the structure and function of the hippocampus that may be significantly associated with cognitive function.

Official Title
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The Effect of Metformin Treatment on Cognitive Impairment in Patients With Schizophrenia Co-morbid Metabolic Syndrome: a Prospective Cohort Study

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the Diagnostic and Statistical Manual (DSM-5) diagnostic criteria for schizophrenia; Duration of illness less than 5 years with current symptoms exacerbation; Male and female aged 18 to 65 years; PANSS total score < 60 and CDSS-C total score < 6; Signed the study consent for participation; Patients with higher risk factors for MetS, or patients who gained weight > 10% of their pre-drug weight within the first year after antipsychotic medication. Exclusion Criteria: Having a history of substance dependence or abuse or whose symptoms are caused by other diagnosable mental disorders; Having a history of traumatic brain injury, seizures, or other known neurological or organic diseases of the central nervous system; Taking antidepressants, stimulants, mood stabilizers or accepting electricity shock treatment; Having current suicidal or homicidal thoughts or any safety concern by research staff that cannot be managed in an inpatient setting; The routine blood tests showing abnormal renal, and liver function; Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two groups were observed longitudinally for 24 weeks.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: metformin treatment<br> | Drug: metformin<br>* metformin 1500mg per day<br>|
| No Intervention: non-metformin treatment<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive improvement will be assessed using the MATRICS Consensus Cognitive Battery (MCCB) composite score | The investigators will use the MATRICS Consensus Cognitive Battery (MCCB) Composite score as primary cognitive outcome measure before and after treatment at different follow up point. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of clinical symptoms by PANSS | The change of Positive And Negative Syndrome Scale (PANSS) total, positive and negative symptoms before and after treatment at different follow up point. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Metabolic syndrome, Metformin, Cognitive impairment, Clinical trial