Clinical trial NCT03451734: Optimizing and Individualizing the Pharmacological Treatment of First-episode Schizophrenic Patients
Official title: Optimizing and Individualizing the Pharmacological Treatment of First-episode Schizophrenic Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Schizophrenia
Metabolic Syndrome
Keywords: Optimized and individualized antipsychotic treatment
Side Effect
Efficacy
Biomarker
Lead sponsor: Central South University
Sponsor class: OTHER
Collaborators: name: Xiangya Hospital of Central South University
name: Shanghai Mental Health Center
name: West China Hospital
name: First Affiliated Hospital of Zhejiang University
name: Air Force Military Medical University, China
name: Jiangsu Province Nanjing Brain Hospital
name: First Affiliated Hospital of Harbin Medical University
name: Shanxi Medical University
name: First Affiliated Hospital of Kunming Medical University
name: Guangzhou Mental Hospital
name: First Affiliated Hospital of Chongqing Medical University
name: Capital Medical University
name: China Medical University, China
name: The First Affiliated Hospital of Zhengzhou University
name: First Affiliated Hospital Xi'an Jiaotong University
name: Hebei Medical University
name: Shenzhen Mental Health Center
name: Sun Yat-sen University
name: Wuhan Mental Health Centre
name: Shanghai Jiao Tong University School of Medicine
First posted: 2018-03-02
Enrollment: 2000
Sex: ALL
Minimum age (years): 17
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Meet the Diagnostic and Statistical Manual (DSM-V) diagnostic criteria for schizophrenia;Duration of illness less than 3 years with current symptoms exacerbation;Male and female with aged 17 to 65 years;

Brief summary: The study is performed in 20 different hospitals from 19 cities in China. Three sub-projects are included. About sub-project 1, we build a clinical database system and a biological sample bank for data and samples management, which is applicable in other hospitals in this project. 1800 first-episode schizophrenia patients will be recruited in 19 sites and randomized into 6 treatment groups (olanzapine, risperidone, aripiprazole, ziprasidone, amisulpride, haloperidol). Through 8-week treatment and follow-up, we collect multidimensional indexes from psychopathology, neuropsychology, brain imaging, physiology, biochemistry, and life stress data. The summarized data is analyzed to screen potential biomarkers or biomarker panel that may predict the antipsychotic response, and ultimately to establish a prediction model.Sub-project 2, as an extension of sub-project 1, includes verification of the prediction model established in sub-project 1 and optimization of the current therapy with add-on treatment. Firstly, the validation process of the prediction model undergoes with an independent patient cohort. Next, we apply the add-on treatment to the patients who don't have ideal response to antipsychotic treatment after 8-week treatment. According to the results above, we manage to construct an optimized and individualized therapy for schizophrenia.In the end,We tend to conduct a randomized double-blind controlled trial to assess the safety and efficacy of the combination strategy for antipsychotic-induced metabolism syndrome, which includes metformin and lifestyle intervention. In the meanwhile, for schizophrenia patients at high-risk of metabolic syndrome, we tend to establish a prevention strategy expected to reduce or delay the occurrence of metabolic syndrome, which includes low-dose metformin and lifestyle intervention. We hope to successfully construct a comprehensive intervention strategy on metabolic syndrome induced by antipsychotic medications.

Detailed description: For sub-project1 and 2:Inclusion criteria: Participants are ineligible to enter the trial under the following conditions: 1) Participants must be aged 18 to 65 years old who meet the criteria for schizophrenia diagnosed by Diagnostic and Statistical Manual of Mental Disorders-fifth edition (DSM-5) or International Classification of Diseases- tenth edition (ICD-10); 2) participants are in current episode of psychotic symptoms with a disease course less than 3 years and intermission less than 6 months; 3). there is at least 1 guardian to accompany patient within 1 year; 4). Participants and their guardians must sign an Informed Consent Form (ICF) indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.

Exclusion criteria (any potential paticipant who meets any of the following criteria will be excluded from participating in the study): 1). Participants with known or suspected clinically unstable systemic medical disorder; 2). participant has a current or prior DSM-5/ ICD-10 diagnosis of substance use disorder, intellectual disability, autism spectrum disorder, dementia or severe cognitive impairment; 3). planning to be pregnant, pregnancy or breast-feeding; 4). currently enrolled in another clinical trial.

For sub-project 3:The diagnostic criteria for Paticipants who develop metabolic syndrome: A. body mass index ≥ 25.0kg / m2; B. hyperglycemia: fasting blood glucose ≥ 110mg/dl (6.1mmol/l) and / or plasma glucose ≥ 140mg/dl(7.8mmol/l) after glucose load; and / or those who have been diagnosed with diabetes and received treatment; C. hypertension: systolic blood pressure (SBP) / diastolic blood pressure (DBP) ≥ 140/90mmHg, and / or those who have been diagnosed as hypertension and received treatment; D. dyslipidemia: at fasting state, total cholesterol (TG) ≥ 150 mg/dl (1.7mmol/l); and / or HDL-C: male \< 35mg/dl (0.9mmol/l), female \< 39mg/dl (1.0mmol/l) . The inclusive criteria for patients at high-risk of MetS: A. paticipants are taking antipsychotic drugs that significantly affect metabolisms, such as olanzapine, clozapine or risperidone; B. paticipants have family history of diabetes, hypertension and heart disease; C. the age of paticipants is over 40 years old; D. paticipants have no nonalcoholic fatty liver and gout; E. paticipants who have one or two components of metabolic syndrome but do not meet the diagnostic criteria.

For clinical and biological data collection, we collect blood samples and case information, which contains demographic data, medical history (including current medical history, past history, personal history and family history), medication regimen and results of follow-up evaluation. The biological samples are stored using unique code whose storage information can be linked to research case in the web server.

The Standard Operations Procedures (SOPs) are followed for data collection, storage, tracking, and utilization.

Professional technicians are employed for the establishment and subsequent maintenance of Internet platform, including web server and mobile terminal applications (APP). Ancillary researchers are involved for collection and timely upload of case information online. Principal investigators are responsible for auditing the data and quality control.

Eligibility criteria: Inclusion Criteria:

1. Meet the Diagnostic and Statistical Manual (DSM-V) diagnostic criteria for schizophrenia;
2. Duration of illness less than 3 years with current symptoms exacerbation;
3. Male and female with aged 17 to 65 years;
4. Signed the study consent for participation

Exclusion Criteria:

1. Having history of substance dependence or abuse or whose symptoms are caused by the other diagnosable mental disorders;
2. Having history of traumatic brain injury, seizures or other known neurological or organic diseases of the central nervous system;
3. Taking antidepressants, stimulants, mood stabilizer or accepts electricity shock treatment;
4. Having current suicidal or homicidal thoughts or any safety concern by research staff that cannot be manage in an inpatient setting;
5. The routine blood tests showing abnormal renal, liver function;
6. Pregnant or lactating women.
7. No administration of any antibiotics in a mouth

Primary outcomes:
measure: Positive And Negative Syndrome Scale (PANSS)
timeFrame: 8 weeks
measure: Clinical Global Impressions(CGI)
timeFrame: 8 weeks
measure: Global Assessment Function(GAF)
timeFrame: 8 weeks
measure: MATRICS Consensus Cognitive Battery (MCCB) composite score
timeFrame: 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Changsha
country: China
facility: Mental Health Institute of 2nd Xiangya Hospital,CSU
state: Hunan
Study officials:
References:
citation: Xiao J, Huang J, Long Y, Wang X, Wang Y, Yang Y, Hei G, Sun M, Zhao J, Li L, Shao T, Wang W, Kang D, Liu C, Xie P, Huang Y, Wu R, Zhao J. Optimizing and Individualizing the Pharmacological Treatment of First-Episode Schizophrenic Patients: Study Protocol for a Multicenter Clinical Trial. Front Psychiatry. 2021 Feb 25;12:611070. doi: 10.3389/fpsyt.2021.611070. eCollection 2021.
citation: Peng XJ, Hei GR, Li RR, Yang Y, Liu CC, Xiao JM, Long YJ, Shao P, Huang J, Zhao JP, Wu RR. The Association Between Metabolic Disturbance and Cognitive Impairments in Early-Stage Schizophrenia. Front Hum Neurosci. 2021 Feb 22;14:599720. doi: 10.3389/fnhum.2020.599720. eCollection 2020.
citation: Huang J, Hei GR, Yang Y, Liu CC, Xiao JM, Long YJ, Peng XJ, Yang Y, Zhao JP, Wu RR. Increased Appetite Plays a Key Role in Olanzapine-Induced Weight Gain in First-Episode Schizophrenia Patients. Front Pharmacol. 2020 May 22;11:739. doi: 10.3389/fphar.2020.00739. eCollection 2020.