5-HTR2A, DRD2,and COMT Genes Polymorphisms and Olanzapine Plasma Concentration in Treatment of Early-onset Schizophrenia

Effects of 5-HTR2A, DRD2,and COMT Genes Polymorphisms and Drug Plasma Concentration on Antipsychotic Response to Olanzapine in Treatment of Early-onset Schizophrenia

In this study,investigators will recruit 100 DSM-Ⅴdefined EOS Han patients, older than 7 years old and onset of illness before 17 years old, and all EOS patients will receive a 8-week systematic olanzepine titration treatment and a battery of assessments of treatment effect and safety. Blood olanzepine plasma concentration will be tested regularly and genotyping of 8 polymorphisms of 5-HTR2A, DRD2 and COMT genes will be conducted by Polymerase Chain Reaction （PCR）, Restriction Fragment Length Polymorphism (RFLP) and TaqMan probes genotyping technology. The aim of the study is to explore the predictive factors on olanzepine treatment response in EOS, which can guide the individualized treatment and improve the cure rate of EOS in clinical setting.

Study Overview

• Status: Completed
• Conditions: Early-onset Schizophrenia
• Intervention / Treatment: Drug: olanzapine

Detailed Description

Early-onset schizophrenia (EOS) is the World Health Organization ranked psychosis as the third most disabling condition worldwide in youth, and may lead to obvious social dysfunction and interfere seriously with neurodevelopmental processes in a young person, which in turn has the potential to irreversibly alter the trajectory of his or her life. To improve the outcome of the patients of EOS, elaborate and individualized therapeutic regimen is urgently needed. The functional gene polymorphisms and drug (antipsychotics) plasma concentration can both influence the drug response, but few studies explore the contributions of genetic heterogeneity, drug plasma concentration and clinical features of patients to drug response together and interactions of above factors in EOS patients. In this study investigators will recruit 100 DSM-Ⅴdefined EOS Han patients, older than 7 years old and onset of illness before 17 years old, and all EOS patients will receive a 8-week systematic olanzepine titration treatment and a battery of assessments of treatment effect and safety. Blood olanzepine plasma concentration will be tested regularly and genotyping of 8 polymorphisms of 5-HTR2A, DRD2 and COMT genes will be conducted by Polymerase Chain Reaction （PCR）, Restriction Fragment Length Polymorphism (RFLP) and TaqMan probes genotyping technology. The aim of the study is to explore the predictive factors on olanzepine treatment response in EOS, which can guide the individualized treatment and improve the cure rate of EOS in clinical setting.

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Yunnan
    • Kunming, Yunnan, China, 650032
      • Psychiatry Department,First Affiliated Hospial Of Kunming Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• above 7 years old,
• age of onset ≤17 years old,
• Han or other nationality, male or female,
• in line with the diagnostic DSM-V criteria for schizophrenia, and
• negative and positive symptom scale (Positive and Negative Syndrome Scale, PANSS) score ≥70 points;
• patients are in the condition of first-episode, or relapse.

Exclusion Criteria:

• IQ <70,
• current or previous history of traumatic brain injury,
• psychoactive substance use,
• personality disorders,
• obvious abnormalities on physical and laboratory examination,
• previous allergy or olanzapine had significant adverse reactions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment group; All EOS patients will receive olanzapine treatment with flexible dose(2.5 to 20 mg/day)according to standard body weight,olanzapine will be initiated at 2.5 or 5 mg/day and the dose could be increased by 2.5 or 5 mg/day dose increments at the investigator's discretion.A effective dose would be titrated in two weeks with no tolerability or safety issues are apparent,the investigator could decrease the dose at any time and in any number of dose decrements if patients experienced an adverse event.

Drug: olanzapine; olanzapine will be initiated at 2.5 or 5 mg/day according to patient's weight, and the dose could be increased by 2.5 or 5 mg every 4-7days at the investigator's discretion.A effective dose would be titrated in two weeks with no tolerability or safety issues are apparent,; Other Names: Zyprexa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
multiple regression equation of 5-HTR2A、DRD2 and COMT Genes Polymorphisms and Olanzapine Plasma Concentration and clinical features	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
change in score of PANSS	baseline and 12 weeks
plateau concentration of olanzapine	2 or 3,12 weeks
change in Serum prolactin levels	12 weeks
Prevalence associated with age、gender and onset form	12 weeks

Collaborators and Investigators

• Sponsor: Kunming Medical University
• Collaborators: National Natural Science Foundation of China
• Investigators: Principal Investigator: Xu xiufeng, Psychiatry Department ,First Affiliated Hospital Of Kunming Medical University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: April 28, 2015
• First Submitted That Met QC Criteria: May 5, 2015
• First Posted (Estimate): May 6, 2015

Study Record Updates

• Last Update Posted (Actual): March 2, 2021
• Last Update Submitted That Met QC Criteria: February 27, 2021
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Genes Polymorphisms; Plasma Concentration
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Olanzapine
• Other Study ID Numbers: 81460218

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No