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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| metformin treatment | Other |
| |
| non-metformin treatment | No Intervention |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| metformin | Drug | metformin 1500mg per day |
|
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Depression by CDSS-C | The investigators will assess depression by Calgary Depression Scale for Schizophrenia (Chinese version, CDSS-C) | 12 weeks |
| Biological markers will be measured by ELISA | The oxidative stress indexes and inflammatory biomarkers will measured by Enzyme-linked Immuno Sorbent Assay (ELISA). |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Tiannan Shao, M.D., Ph.D. | Contact | +86 13341318057 | shaostndoc@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Tiannan Shao, M.D., Ph.D. | Central South University | Principal Investigator |
| Dongyu Kang, M.D. | Central South University | Principal Investigator |
| Renrong Wu, M.D., Ph.D. |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Second Xiangya Hospital of Central South University | Recruiting | Changsha | Hunan | 410011 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23106932 | Background | Lindenmayer JP, Khan A, Kaushik S, Thanju A, Praveen R, Hoffman L, Cherath L, Valdez G, Wance D. Relationship between metabolic syndrome and cognition in patients with schizophrenia. Schizophr Res. 2012 Dec;142(1-3):171-6. doi: 10.1016/j.schres.2012.09.019. Epub 2012 Oct 26. | |
| 28032535 | Background | Bora E, Akdede BB, Alptekin K. The relationship between cognitive impairment in schizophrenia and metabolic syndrome: a systematic review and meta-analysis. Psychol Med. 2017 Apr;47(6):1030-1040. doi: 10.1017/S0033291716003366. Epub 2016 Dec 29. |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D024821 | Metabolic Syndrome |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
| D007333 | Insulin Resistance |
| D006946 | Hyperinsulinism |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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Two groups were observed longitudinally for 24 weeks.
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| 12 weeks |
| Central South University |
| Study Chair |
| 25470390 | Background | Ying MA, Maruschak N, Mansur R, Carvalho AF, Cha DS, McIntyre RS. Metformin: repurposing opportunities for cognitive and mood dysfunction. CNS Neurol Disord Drug Targets. 2014;13(10):1836-45. doi: 10.2174/1871527313666141130205514. |
| 40597190 | Derived | Cai J, Xiao J, Long Y, Cao T, Lin C, Hei G, Wang W, Kang D, Huang J, Shao T, Cai H, Wu R. Metformin-improved cognitive impairment in patients with schizophrenia is correlated with activation of tricarboxylic acid cycle and restored functional connectivity of hippocampus. BMC Med. 2025 Jul 1;23(1):349. doi: 10.1186/s12916-025-04218-4. |
| 37821461 | Derived | Shao T, Huang J, Zhao Y, Wang W, Tian X, Hei G, Kang D, Gao Y, Liu F, Zhao J, Liu B, Yuan TF, Wu R. Metformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortex. Transl Psychiatry. 2023 Oct 11;13(1):315. doi: 10.1038/s41398-023-02616-x. |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |