Optimizing and Individualizing the Pharmacological Treatment of First-episode Schizophrenic Patients

NCT03451734 | Completed

• 1 other identifier: 2016YFC1306900
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia; Metabolic Syndrome

Keywords

Optimized and individualized antipsychotic treatment; Side Effect; Efficacy; Biomarker

Outcome Measures

Primary Outcomes (4)

• Positive And Negative Syndrome Scale (PANSS)

  The change of Positive And Negative Syndrome Scale (PANSS) total, positive and negative symptoms before and after treatment at different follow up point.

  8 weeks

• Clinical Global Impressions(CGI)

  The change of Clinical Global Impressions(CGI):severity of illness(SI), global improvement(GI) and efficacy index(EI) before and after treatment at different follow up point.

  8 weeks

• Global Assessment Function(GAF)

  The change of Global Assessment Function(GAF) before and after treatment at different follow up point.

  8 weeks

• MATRICS Consensus Cognitive Battery (MCCB) composite score

  The investigators will use the MATRICS Consensus Cognitive Battery (MCCB) Composite score as primary cognitive outcome measure before and after treatment at different follow up point.

  8 weeks

Study Arms (5)

treatment cohort

in sub-project 1, participants are randomized into olanzapine, risperidone, aripiprazole, amisulpride, ziprasidone, and haloperidol groups, we give them evaluation, and adjust dose of medication and deal with side effect if necessary.

Drug: antipsychotic medications

adjunctive group

Patients who do not have an ideal response to antipsychotics treatment (reduction rate of Positive and Negative Symptom Scale (PANSS) score less than 25%) in sub-project 2 are recruited in this trial. They are randomly assigned to 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, and the antipsychotic drugs used at this stage are still consistent with the first trial of sub-project 2. At baseline, 4 weeks and 8 weeks after treatment, all participants receive evaluations.

Drug: adjunctive group

metformin and lifestyle intervention for MetS

Participants who develop MetS at the last visit in sub-project 1 and sub-project 2 are recruited in this trial. Patients are randomized into low-dose metformin (1000 mg/d), high-dose metformin (1500 mg/d), low dose metformin plus lifestyle intervention group (1000 mg/d), high dose metformin plus lifestyle intervention (1500 mg/d), lifestyle intervention, and placebo groups. The timepoints of the visits are at baseline, the 4th week, the 8th week, and the 12th week.

Drug: metformin and lifestyle intervention

metformin and lifestyle prevention for high risk of MetS

Participants who are at a high risk of MetS are recruited in this trial. Participants are randomized into low dose metformin (750 mg/d), high dose metformin (1000 mg/d), lifestyle intervention, and placebo groups. The timepoints of the visits are at baseline, the 4th week, the 8th week, and the 12th week.

Drug: metformin and lifestyle intervention

validation cohort

in sub-project 2, there are1,800 first-episode schizophrenia patients recruited from 19 hospitals, and six groups as with sub-project 1. The assessments (timepoint and content) are conducted as in sub-project 1.

Drug: antipsychotic medications

Interventions

antipsychotic medications DRUG

olanzapine, risperidone, aripiprazole, amisulpride, ziprasidone, and haloperidol groups

treatment cohort; validation cohort

adjunctive group DRUG

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.

adjunctive group

metformin and lifestyle intervention DRUG

different dose metformin combines lifestyle intervention

metformin and lifestyle intervention for MetS; metformin and lifestyle prevention for high risk of MetS

Eligibility Criteria

• Age: 17 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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;

You may qualify if:

• 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;
• Signed the study consent for participation

You may not qualify if:

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

Sponsors & Collaborators

• Central South University: lead
• Xiangya Hospital of Central South University: collaborator
• Shanghai Mental Health Center: collaborator
• West China Hospital: collaborator
• First Affiliated Hospital of Zhejiang University: collaborator
• Air Force Military Medical University, China: collaborator
• Jiangsu Province Nanjing Brain Hospital: collaborator
• First Affiliated Hospital of Harbin Medical University: collaborator
• Shanxi Medical University: collaborator
• First Affiliated Hospital of Kunming Medical University: collaborator
• Guangzhou Mental Hospital: collaborator
• First Affiliated Hospital of Chongqing Medical University: collaborator
• Capital Medical University: collaborator
• China Medical University, China: collaborator
• The First Affiliated Hospital of Zhengzhou University: collaborator
• First Affiliated Hospital Xi'an Jiaotong University: collaborator
• Hebei Medical University: collaborator
• Shenzhen Mental Health Center: collaborator
• Sun Yat-sen University: collaborator
• Wuhan Mental Health Centre: collaborator
• Shanghai Jiao Tong University School of Medicine: collaborator

Study Sites (1)

Mental Health Institute of 2nd Xiangya Hospital,CSU

Changsha, Hunan, 410011, China

Location

Related Publications (7)

• Gao S, Xu Q, Han Y, Jiang J, Wu F, Peng T, Ling C, Ni S, Zhang R, Ming Y, Liu X, Xu X. Relationship between cognitive impairments and psychopathological symptoms in female schizophrenia subsequent to 8 weeks treatment with antipsychotic drugs. BMC Psychiatry. 2025 Mar 7;25(1):211. doi: 10.1186/s12888-025-06605-w.

  PMID: 40055632 DERIVED

• Xie P, Shao T, Long Y, Xie W, Liu Y, Yang Y, Huang Y, Wu R, Deng Q, Tang H. Orlistat for the treatment of antipsychotic-induced weight gain: an eight-week multicenter, randomized, placebo-controlled, double-blind trial. Lipids Health Dis. 2024 Jul 24;23(1):225. doi: 10.1186/s12944-024-02214-w.

  PMID: 39049073 DERIVED

• Zeng J, Zhang W, Lu X, Zhou H, Huang J, Xu Z, Liao H, Liang J, Liang M, Ye C, Sun T, Hu Y, She Q, Chen H, Guo Q, Yan L, Wu R, Li Z. The association of SOD and HsCRP with the efficacy of sulforaphane in schizophrenia patients with residual negative symptoms. Eur Arch Psychiatry Clin Neurosci. 2024 Aug;274(5):1083-1092. doi: 10.1007/s00406-023-01679-7. Epub 2023 Sep 20.

  PMID: 37728803 DERIVED

• Long Y, Wu Q, Yang Y, Cai J, Xiao J, Liu Z, Xu Y, Chen Y, Huang M, Zhang R, Xu X, Hu J, Liu Z, Liu F, Zheng Y, Meng H, Wang Z, Tang Y, Song X, Chen Y, Wang X, Liu T, Wu X, Fang M, Wan C, Zhao J, Wu R. Early non-response as a predictor of later non-response to antipsychotics in schizophrenia: a randomized trial. BMC Med. 2023 Jul 19;21(1):263. doi: 10.1186/s12916-023-02968-7.

  PMID: 37468932 DERIVED

• 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.

  PMID: 33716817 DERIVED

• 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.

  PMID: 33692676 DERIVED

• 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.

  PMID: 32528286 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

blood,serum.

MeSH Terms

Conditions

Schizophrenia; Metabolic Syndrome

Interventions

Metformin

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D,Ph.D,Professor

Study Record Dates

• First Submitted: January 23, 2018
• First Posted: March 2, 2018
• Study Start: January 23, 2018
• Primary Completion: June 30, 2021
• Study Completion: June 30, 2021
• Last Updated: August 12, 2021

Record last verified: 2021-08

Locations

CN (1)