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

NCT ID: NCT03271866

Last Updated: 2023-04-11

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-28
• Study Completion Date: 2023-12-31

Brief Summary

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

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.

Conditions

Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

metformin treatment

Group Type: OTHER

metformin

Intervention Type: DRUG

metformin 1500mg per day

non-metformin treatment

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

metformin

metformin 1500mg per day

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Meet the Diagnostic and Statistical Manual (DSM-5) diagnostic criteria for schizophrenia;

2. Duration of illness less than 5 years with current symptoms exacerbation;

3. Male and female aged 18 to 65 years;

4. PANSS total score < 60 and CDSS-C total score < 6;

5. Signed the study consent for participation;

6. 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

1. Having a history of substance dependence or abuse or whose symptoms are caused by other diagnosable mental disorders;

2. Having a history of traumatic brain injury, seizures, or other known neurological or organic diseases of the central nervous system;

3. Taking antidepressants, stimulants, mood stabilizers or accepting electricity shock treatment;

4. Having current suicidal or homicidal thoughts or any safety concern by research staff that cannot be managed in an inpatient setting;

5. The routine blood tests showing abnormal renal, and liver function;

6. Pregnant or lactating women.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Central South University

OTHER

Sponsor Role: lead

Responsible Party

Renrong Wu

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tiannan Shao, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Central South University

Dongyu Kang, M.D.

Role: PRINCIPAL_INVESTIGATOR

Central South University

Renrong Wu, M.D., Ph.D.

Role: STUDY_CHAIR

Central South University

Locations

The Second Xiangya Hospital of Central South University

Changsha, Hunan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Tiannan Shao, M.D., Ph.D.

Role: CONTACT

shaostndoc@163.com

+86 13341318057

Facility Contacts

Tiannan Shao, M.D., Ph.D.

Role: primary

shaostndoc@163.com

+86 13341318057

Renrong Wu, M.D., Ph.D.

Role: backup

wurenrong2013@163.com

References

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.

Reference Type: BACKGROUND

PMID: 23106932 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28032535 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25470390 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 40597190 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37821461 (View on PubMed)

Other Identifiers

WU201708MET

Identifier Type: -

Identifier Source: org_study_id