Clinical trial NCT03271866: Metformin Treatment on Cognitive Impairment of Schizophrenia Co-morbid Metabolic Syndrome
Official title: The Effect of Metformin Treatment on Cognitive Impairment in Patients With Schizophrenia Co-morbid Metabolic Syndrome: a Prospective Cohort Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Schizophrenia
Keywords: Schizophrenia
Metabolic syndrome
Metformin
Cognitive impairment
Clinical trial
Lead sponsor: Central South University
Sponsor class: OTHER
First posted: 2017-09-05
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two groups were observed longitudinally for 24 weeks.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Cognitive improvement will be assessed using the MATRICS Consensus Cognitive Battery (MCCB) composite score
timeFrame: 12 weeks
Secondary outcomes:
measure: Change of clinical symptoms by PANSS
timeFrame: 12 weeks
Other outcomes:
measure: Depression by CDSS-C
timeFrame: 12 weeks
measure: Biological markers will be measured by ELISA
timeFrame: 12 weeks
Locations:
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
Study officials:
affiliation: Central South University
name: Tiannan Shao, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Central South University
name: Dongyu Kang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Central South University
name: Renrong Wu, M.D., Ph.D.
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.