Metformin Treatment on Cognitive Impairment of Schizophrenia

NCT05838573 | Recruiting Phase 3

• 1 other identifier: WU202211MET
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 4

Brief Summary

In this study, the investigators will investigate the effect and the underlying mechanism of metformin treatment on cognitive impairment in individuals with schizophrenia. The study will recruit 120 individuals with schizophrenia at 4 sites, who will be randomized to metformin or placebo group for 24-week treatment. Clinical assessments will be done at screen/baseline, 12th week and 24th week. Participants who don't meet any of the diagnostic criteria for metabolic syndrome will only accept baseline evaluations. The specific aims are to compare healthy volunteers versus schizophrenic participants on:1) cognition; 2) MRI features, and to compare metformin group versus placebo group of 24-week treatment cohort on: 1) cognition; 2) clinical core symptoms; 3) MRI features. Biological samples also will be collected and stored to explore related mechanisms.

Conditions

Schizophrenia

Keywords

Schizophrenia; Cognitive impairment; Metformin; Clinical trial

Outcome Measures

Primary Outcomes (2)

• Changes of the score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery of interventional participants

  At baseline and 12th week, the cognitive function of interventional participants will be assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. Evaluator convert raw scores to scale scores, then to normalized T scores. T scores of seven domains and composite score are further calculated. The changes of scores after 12-week metformin treatment will be used for assessing the improvement of cognitive function (higher score means better function).

  From baseline to 12th week；From baseline to 24th week；

• Changes of brain cerebral blood flow by arterial spin labeling of interventional participants

  At baseline and 12th week, whole brain cerebral blood flow (CBF) will be recorded by arterial spin labeling (ASL). For interventional participants, the changes in CBF (c-CBF) before and after the application of 160 units nasal insulin spray of interventional participants will be calculated. The changes of c-CBF after 12-week metformin treatment will be reported.

  From baseline to 12th week；From baseline to 24th week

Secondary Outcomes (8)

• Changes of resting-state functional MRI of interventional participants

  From baseline to 12th week; From baseline to 24th week

• Changes of social function by Personal and Social Performance Scale

  From baseline to 24th week

• Changes of clinical symptoms by Scale for Assessment of Negative Symptoms

  From baseline to 24th week

• Changes of clinical symptoms by Positive And Negative Syndrome Scale

  From baseline to 24th week

• Changes of homoeostasis model assessment-estimated insulin resistance

  From baseline to 24th week

Other Outcomes (3)

• High-resolution T1-weighted anatomical images and Diffusion Tensor Imaging by MRI at baseline for predicting efficacy

  From baseline to 24th week

• The difference of Diffusion Tensor Imaging scanned by MRI between schizophrenic participants and healthy volunteers

  Baseline

• Safety evaluation through the Systematic Assessment for Treatment Emergent Events

  From baseline to 24th week

Study Arms (4)

Metformin group

ACTIVE COMPARATOR

The goal is to investigate whether adding metformin will benefit the cognitive impairment in individuals with schizophrenia.

Drug: Metformin treatment

Placebo group

PLACEBO COMPARATOR

The purpose of using placebo is to judge if the outcome is related to the study medication rather than other reasons.

Drug: Placebo treatment

Cross-sectional participants

EXPERIMENTAL

Participants do not meet any of the diagnostic criteria for metabolic syndrome: 1)abdominal obesity (i.e. central obesity): waist circumference for male≥90 cm, for female ≥85 cm; 2)fasting blood glucose ≥110 mg/dl (6.1 mmol/l) and/or plasma glucose ≥140 mg/dl (7.8 mmol/l) after glucose load; 3)at fasting state, triglyceride ≥1.7 mmol/l; 4)at fasting state, HDL-C \<1.04 mmol/L. the other inclusion criteria and exclusion criteria are same as the intervention group.

Other: Baseline assessments

Healthy volunteer

EXPERIMENTAL

Other: Volunteer assessments

Interventions

Metformin treatment DRUG

Participants assigned to the metformin group will receive 500mg metformin three times daily (tid) for 24 weeks. The initial dose will be 500 mg orally in the evening for the first two days, followed by an increase to 500mg twice a day for the subsequent two days. By day 5, the dosage will be further increased to 500mg tid. The highest tolerated dosage will be maintained for participants who could not tolerate the maximum dosage.

Metformin group

Placebo treatment DRUG

Parallel-dose adjustments will be made for the placebo group to maintain consistency in dosing between the two groups.

Placebo group

Baseline assessments OTHER

Schizophrenic participants who don't meet any of the diagnostic criteria for metabolic syndrome will only accept baseline evaluations.

Cross-sectional participants

Volunteer assessments OTHER

Apart from psychiatry scales(Hamilton Depression Scale, Young Mania Rating Scale and Self-reporting Inventory-90), other assessments for the healthy subjects are the same as the baseline for sczhiophrenic participants.

Healthy volunteer

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female aged 18 to 50 years, who meet the Diagnostic and Statistical Manual (DSM-5) diagnostic criteria for schizophrenia.
• Duration of illness less than 15 years with current symptoms in a stable condition.
• Participants must be receiving stable treatment with standard-of-care medications, with a maximum allowance of two antipsychotic medications. If additional anticholinergic agents are required for the management of extrapyramidal symptoms, they should be prescribed at low dosages.
• Have great compliance with medication and follow-up.
• Meet one of the diagnostic criteria for metabolic syndrome: 1)abdominal obesity (i.e. central obesity): waist circumference for male≥90 cm, for female ≥85 cm; 2)fasting blood glucose ≥110 mg/dl (6.1 mmol/l) and/or plasma glucose ≥140 mg/dl (7.8 mmol/l) after glucose load; 3)at fasting state, triglyceride ≥1.7 mmol/l; 4)at fasting state, HDL-C \<1.04 mmol/L.
• Signed the study consent for participation.

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 accepts electricity shock treatment.
• Having current suicidal or homicidal thoughts or any safety concern by research staff that cannot be managed in an inpatient setting.
• Taking dementia related drugs, minocycline, and other drugs that could affect cognitive function.
• The routine blood tests showing significant abnormal renal, liver function or other somatic disease.
• Pregnant or lactating women.
• For schizophrenic participants who don't meet any of the diagnostic criteria for metabolic syndrome will only accept baseline evaluations.

Sponsors & Collaborators

• The Second People's Hospital of Dali Bai Autonomous Prefecture: collaborator
• The Third people's Hospital of Jiangyin: collaborator
• Central South University: lead
• Shandong Mental Health Center: collaborator

Study Sites (4)

Mental Health Institute of Second Xiangya Hospital,CSU

Changsha, Hunan, 410011, China

RECRUITING

The Third Peoples's Hospital of Jiangyin

Jiangyin, Jiangsu, 214400, China

RECRUITING

Shandong Mental Health Center

Jinan, Shandong, 250014, China

RECRUITING

The Second People's Hospital of Dali Bai Autonomous Prefecture

Dali, Yunnan, 671014, China

RECRUITING

MeSH Terms

Conditions

Schizophrenia; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders

Study Officials

• Renrong Wu, M.D., Ph.D.

  Mental Health Institute of Second Xiangya Hospital,CSU

  STUDY CHAIR

Central Study Contacts

Jing Huang, M.D.

CONTACT

15874290980; jinghuangserena@csu.edu.cn

Jingmei Xiao, M.D.

CONTACT

17673129702; xiaojingmei0413@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: March 22, 2023
• First Posted: May 1, 2023
• Study Start: May 8, 2023
• Primary Completion (Estimated): December 12, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)