Optimizing and Individualizing the Pharmacological Treatment of First-episode Schizophrenic Patients
Condition: Schizophrenia; Metabolic Syndrome
MeSH terms: Metabolic Syndrome; Schizophrenia
Study type: Observational

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.
    

Intervention name(s): antipsychotic medications; adjunctive group; metformin and lifestyle intervention
Intervention type(s): Drug; Drug; Drug
Intervention description(s): olanzapine, risperidone, aripiprazole, amisulpride, ziprasidone, and haloperidol groups; antipsychotic plus placebo, antipsychotic plus sulforaphane(3 tables per day, consisting of 30 mg of SFN-glucosinolate per day), and antipsychotic plus minocycline(200mg per day) groups.; different dose metformin combines lifestyle intervention
Intervention MeSH terms: Metformin; Antipsychotic Agents
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;
      
Biospecimen description: 
      blood,serum.
    
Keywords: Optimized and individualized antipsychotic treatment; Side Effect; Efficacy; Biomarker