The Effect of Metformin Treatment on Cognitive Impairment in Individuals With Schizophrenia: A 24-week Multicentre Randomised Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 120
- 试验地点
- 6
- 主要终点
- Changes of the score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery of interventional participants
研究概览
简要总结
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.
详细描述
Participants screened through inclusion and exclusion criteria will be randomized to metformin or placebo group (2:1). The information of demographic data, medical history, previous and current medication regimen, and family history regarding psychotic and metabolic diseases will be collected at baseline. The assessments will be carried out at baseline, 12th week and 24th week, including physical examination, anthropometry, blood test(blood routine, liver function, renal function, blood lipids, fasting blood glucose, serum insulin and thyroid function), electrocardiogram, MRI scan( High-resolution T1-weighted Anatomical Images, Diffusion Tensor Imaging, Resting-state functional MRI and Arterial Spin Labeling) and psychiatry scales(Positive And Negative Syndrome Scale, Scale for Assessment of Negative Symptoms, Calgary Depressing Scale for Schizophrenia, Personal and Social Performance Scale, The Systematic Assessment for Treatment Emergent Events, the Simpson-Angus Extrapyramidal Side Effects Scale and the Barnes Akathisia Rating Scale); cognitive function will be assessed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia(MATRICS) Consensus Cognitive Battery; biological samples also will be collected and stored to explore related mechanisms. Participants who don't meet any of the diagnostic criteria for metabolic syndrome will only accept baseline evaluations. In addition, we will recruit healthy volunteers, and collect their demographic data, and family history regarding psychotic and metabolic diseases. 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Placebo group
The purpose of using placebo is to judge if the outcome is related to the study medication rather than other reasons.
干预措施: Placebo treatment (Drug)
Healthy volunteer
干预措施: Volunteer assessments (Other)
Cross-sectional participants
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.
干预措施: Baseline assessments (Other)
Metformin group
The goal is to investigate whether adding metformin will benefit the cognitive impairment in individuals with schizophrenia.
干预措施: Metformin treatment (Drug)
结局指标
主要结局
Changes of the score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery of interventional participants
时间窗: From baseline to 12th week；From baseline to 24th week；
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).
Changes of brain cerebral blood flow by arterial spin labeling of interventional participants
时间窗: From baseline to 12th week；From baseline to 24th week
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.
次要结局
- 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)
- 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)
- The difference of cerebral blood flow between schizophrenic participants and healthy volunteers(Baseline)
- The difference of resting-state functional MRI between schizophrenic participants and healthy volunteers(Baseline)
- The difference of the score of the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery between schizophrenic participants and healthy volunteers(Baseline)
研究者
Renrong Wu
Professor
Second Xiangya Hospital of Central South University