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

NCT03271866 | Unknown

• 1 other identifier: WU201708MET
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia

Keywords

Schizophrenia; Metabolic syndrome; Metformin; Cognitive impairment; Clinical trial

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Change of clinical symptoms by PANSS

  12 weeks

Other Outcomes (2)

• Depression by CDSS-C

  12 weeks

• Biological markers will be measured by ELISA

  12 weeks

Study Arms (2)

metformin treatment

OTHER

Drug: metformin

non-metformin treatment

NO INTERVENTION

Interventions

metformin DRUG

metformin 1500mg per day

metformin treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Central South University: lead

Study Sites (1)

The Second Xiangya Hospital of Central South University

Changsha, Hunan, 410011, China

RECRUITING

Related Publications (5)

• 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.

  PMID: 23106932 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.

  PMID: 28032535 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.

  PMID: 25470390 BACKGROUND

• 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.

  PMID: 40597190 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.

  PMID: 37821461 DERIVED

MeSH Terms

Conditions

Schizophrenia; Metabolic Syndrome; Cognitive Dysfunction

Interventions

Metformin

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Cognition Disorders; Neurocognitive Disorders

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• 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.

  Central South University

  STUDY CHAIR

Central Study Contacts

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

CONTACT

+86 13341318057; shaostndoc@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Two groups were observed longitudinally for 24 weeks.

Study Record Dates

• First Submitted: August 30, 2017
• First Posted: September 5, 2017
• Study Start: August 28, 2017
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: April 11, 2023

Record last verified: 2023-04

Locations

CN (1)