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Identification of Multi-modal Bio-markers for Early Diagnosis and Treatment Prediction in Schizophrenia Individuals

Primary Purpose

Schizophrenia, Major Depressive Disorder, Anxiety Disorders

Status
Unknown status
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
Risperidone
Olanzapine
Aripiprazole
Sponsored by
Tianjin Medical University General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Schizophrenia focused on measuring Precision medicine, Bio-marker, Neuroimaging, Molecular genetics, Neurobiochemical, Early diagnosis, Early prediction

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria for patients:

  • According with American mental disorder diagnosis and Diagnostic criteria for schizophrenia, major depressive disorder, and anxiety disorder in the statistical manual DSM-IV
  • The time from the onset of symptoms for the first time to participate in study is less than 12 months
  • No any anti-psychotic drugs or medication was taken more than 14 days
  • Han nationality
  • 18 to 45 years old
  • Right-handed

Inclusion Criteria for healthy controls:

  • Han nationality
  • Right-handedness
  • Gender, age and education level are matched with patients
  • 18 to 45 years old
  • Any mental disorder diagnosis in DSM-IV was excluded
  • There were no relatives with severe mental disorder in the two or three generations

Exclusion Criteria:

  • The patient has other psychiatric disorder beside the illness
  • A history of psychoactive substance use, accompanied by severe physical disease
  • Have a history of epilepsy or coma
  • Women who are pregnant or breast-feeding
  • Accompanied by metal implants, claustrophobia and other contraindications of MRI scan

Sites / Locations

  • Tianjin Medical University General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Risperidone

Olanzapine

Aripiprazole

Arm Description

It can be used after schizophrenia is diagnosed. Risperidone affects prolactin and may affect menstruation in young women, so we will try not to use it in such patients. Patients were randomized to a single Risperidone control trial for 8 weeks to evaluate the clinical efficacy of the patients. Risperidone routine daily 2-6 mg, up to 8 mg, can be taken orally twice a day.

It can be used after schizophrenia is diagnosed. Olanzapine is not generally used in patients with diabetes and hyperlipidemia. Patients were randomized to a single Olanzapine control trial for 8 weeks to evaluate the clinical efficacy of the patients. Olanzapine is available once or twice a day, starting at 5 mg daily and up to 20 mg daily.

It can be used after schizophrenia is diagnosed. Aripiprazole has no specific contraindications. Patients were randomized to a single Aripiprazole control trial for 8 weeks to evaluate the clinical efficacy of the patients. Aripiprazole is taken orally once a day, starting at 10 mg daily and up to 30 mg daily.

Outcomes

Primary Outcome Measures

Positive and Negative Syndrome Scale (PANSS)
It is a scale involved and standardized for assessing the severity of symptoms of different types of schizophrenia. Of the 30 items included in the PANSS, 7 constitute a Positive Scale, 7 a Negative Scale, and the remaining 16 a General Psychopathology Scale. Each of the 30 items is accompanied by a specific definition as well as detailed anchoring criteria for all seven rating points. The scores for these scales are arrived at by summation of ratings across component items. These seven points represent increasing levels of psychopathology, as follows: 1- absent, 2- minimal, 3-mild, 4-moderate, 5-moderate severe, 6-severe, 7-extreme. Therefore, the potential ranges are 7 to 49 for the Positive and Negative Scales, and 16 to 112 for the General Psychopathology Scale. A rating of 7 (extreme) refers to the most serious level of psychopathology in each item, so the higher the score is, the more serious the physical level is.
Clinical Global Impression(CGI)
the CGI is a 3-item observer-rated scale that measures illness severity (CGIS), global improvement or change (CGIC) and therapeutic response.The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients).CGI-C scores range from 1 (very much improved) through to 7 (very much worse). Treatment response ratings should take account of both therapeutic efficacy and treatment-related adverse events and range from 0 (marked improvement and no side-effects) and 4 (unchanged or worse and side-effects outweigh the therapeutic effects). Each component of the CGI is rated separately; the instrument does not yield a global score.

Secondary Outcome Measures

Full Information

First Posted
December 25, 2018
Last Updated
December 27, 2018
Sponsor
Tianjin Medical University General Hospital
Collaborators
Shanghai Mental Health Center, Nanjing Medical University, Tianjin Anding Hospital, Harbin First Specialist Hospital, First Affiliated Hospital of Chongqing Medical University, Anhui Mental Health Center, Wuhan Psychiatric Hospital, Wenzhou Seventh People's Hospital, First Affiliated Hospital of Harbin Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT03790085
Brief Title
Identification of Multi-modal Bio-markers for Early Diagnosis and Treatment Prediction in Schizophrenia Individuals
Official Title
Identification of Multi-modal Bio-markers for Early Diagnosis and Treatment Prediction in Schizophrenia Individuals
Study Type
Interventional

2. Study Status

Record Verification Date
December 2018
Overall Recruitment Status
Unknown status
Study Start Date
September 1, 2018 (Actual)
Primary Completion Date
June 30, 2020 (Anticipated)
Study Completion Date
December 31, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tianjin Medical University General Hospital
Collaborators
Shanghai Mental Health Center, Nanjing Medical University, Tianjin Anding Hospital, Harbin First Specialist Hospital, First Affiliated Hospital of Chongqing Medical University, Anhui Mental Health Center, Wuhan Psychiatric Hospital, Wenzhou Seventh People's Hospital, First Affiliated Hospital of Harbin Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study aims to screen and validate multi-scale bio-markers for early diagnosis and medication monitoring for early schizophrenia, including the genetic, neurobiochemistry, neuroimaging and eletrophysiological measures. Based on the validated bio-markers, the present study further tries to build several prediction models for early differential diagnosis of schizophrenia from healthy controls and other mental diseases (such as the major depression and anxiety disorders), biological sub-typing and diagnosis of the schizophrenia sub-types, and early prediction of the medication effects.
Detailed Description
Schizophrenia is one of the most important diseases that threaten the health of Chinese people. In view of the current lack of objective biological markers in the diagnosis and treatment of schizophrenia, as well as the lack of effective early diagnosis methods and curative effect prediction methods, the investigators carried out joint research by integrating research teams from molecular genetics, neurobiochemistry, psychiatry, medical imaging, information science and other fields. The overall objective of the project is to establish a bio-marker system for individualized diagnosis and treatment of early schizophrenia. Specific research contents include: screening and verifying multidimensional objective biological markers such as genetics, neurobiochemistry, neuroimaging, electrophysiology, which is related to early diagnosis and efficacy prediction of schizophrenia through big data analysis of healthy controls and patients with first episode schizophrenia, depression and anxiety disorder. Pattern recognition method is used to build the individualized early diagnosis model, biological sub-type clustering model, biological sub-type individualized diagnosis model and early curative effect prediction model of schizophrenia. Based on the individualized diagnosis and treatment prediction model of schizophrenia, the individualized diagnosis and treatment toolkit was developed, and the individualized diagnosis and treatment prediction cloud platform was established to provide assist for clinicians.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Major Depressive Disorder, Anxiety Disorders
Keywords
Precision medicine, Bio-marker, Neuroimaging, Molecular genetics, Neurobiochemical, Early diagnosis, Early prediction

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
2700 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Risperidone
Arm Type
Experimental
Arm Description
It can be used after schizophrenia is diagnosed. Risperidone affects prolactin and may affect menstruation in young women, so we will try not to use it in such patients. Patients were randomized to a single Risperidone control trial for 8 weeks to evaluate the clinical efficacy of the patients. Risperidone routine daily 2-6 mg, up to 8 mg, can be taken orally twice a day.
Arm Title
Olanzapine
Arm Type
Experimental
Arm Description
It can be used after schizophrenia is diagnosed. Olanzapine is not generally used in patients with diabetes and hyperlipidemia. Patients were randomized to a single Olanzapine control trial for 8 weeks to evaluate the clinical efficacy of the patients. Olanzapine is available once or twice a day, starting at 5 mg daily and up to 20 mg daily.
Arm Title
Aripiprazole
Arm Type
Experimental
Arm Description
It can be used after schizophrenia is diagnosed. Aripiprazole has no specific contraindications. Patients were randomized to a single Aripiprazole control trial for 8 weeks to evaluate the clinical efficacy of the patients. Aripiprazole is taken orally once a day, starting at 10 mg daily and up to 30 mg daily.
Intervention Type
Drug
Intervention Name(s)
Risperidone
Intervention Description
Risperidone tablet
Intervention Type
Drug
Intervention Name(s)
Olanzapine
Intervention Description
Olanzapine tablet
Intervention Type
Drug
Intervention Name(s)
Aripiprazole
Intervention Description
Aripiprazole tablet
Primary Outcome Measure Information:
Title
Positive and Negative Syndrome Scale (PANSS)
Description
It is a scale involved and standardized for assessing the severity of symptoms of different types of schizophrenia. Of the 30 items included in the PANSS, 7 constitute a Positive Scale, 7 a Negative Scale, and the remaining 16 a General Psychopathology Scale. Each of the 30 items is accompanied by a specific definition as well as detailed anchoring criteria for all seven rating points. The scores for these scales are arrived at by summation of ratings across component items. These seven points represent increasing levels of psychopathology, as follows: 1- absent, 2- minimal, 3-mild, 4-moderate, 5-moderate severe, 6-severe, 7-extreme. Therefore, the potential ranges are 7 to 49 for the Positive and Negative Scales, and 16 to 112 for the General Psychopathology Scale. A rating of 7 (extreme) refers to the most serious level of psychopathology in each item, so the higher the score is, the more serious the physical level is.
Time Frame
30-45 minutes
Title
Clinical Global Impression(CGI)
Description
the CGI is a 3-item observer-rated scale that measures illness severity (CGIS), global improvement or change (CGIC) and therapeutic response.The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients).CGI-C scores range from 1 (very much improved) through to 7 (very much worse). Treatment response ratings should take account of both therapeutic efficacy and treatment-related adverse events and range from 0 (marked improvement and no side-effects) and 4 (unchanged or worse and side-effects outweigh the therapeutic effects). Each component of the CGI is rated separately; the instrument does not yield a global score.
Time Frame
10-15 minutes

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria for patients: According with American mental disorder diagnosis and Diagnostic criteria for schizophrenia, major depressive disorder, and anxiety disorder in the statistical manual DSM-IV The time from the onset of symptoms for the first time to participate in study is less than 12 months No any anti-psychotic drugs or medication was taken more than 14 days Han nationality 18 to 45 years old Right-handed Inclusion Criteria for healthy controls: Han nationality Right-handedness Gender, age and education level are matched with patients 18 to 45 years old Any mental disorder diagnosis in DSM-IV was excluded There were no relatives with severe mental disorder in the two or three generations Exclusion Criteria: The patient has other psychiatric disorder beside the illness A history of psychoactive substance use, accompanied by severe physical disease Have a history of epilepsy or coma Women who are pregnant or breast-feeding Accompanied by metal implants, claustrophobia and other contraindications of MRI scan
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chunshui Yu, MD
Phone
862260363760
Email
chunshuiyu@vip.163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Wen Qin, MD
Phone
862260363760
Email
qinwen@tmu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chunshui Yu, MD
Organizational Affiliation
Tianjin Medical University General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tianjin Medical University General Hospital
City
Tianjin
ZIP/Postal Code
300052
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chunshui Yu, MD
Phone
862260362260
Email
chunshuiyu@vip.163.com
First Name & Middle Initial & Last Name & Degree
Wen Qin, MD
Phone
862260363760
Email
qinwen@tmu.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
29632383
Citation
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Results Reference
result
PubMed Identifier
28521048
Citation
Zhu J, Zhuo C, Xu L, Liu F, Qin W, Yu C. Altered Coupling Between Resting-State Cerebral Blood Flow and Functional Connectivity in Schizophrenia. Schizophr Bull. 2017 Oct 21;43(6):1363-1374. doi: 10.1093/schbul/sbx051.
Results Reference
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27918562
Citation
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Results Reference
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PubMed Identifier
26619358
Citation
Jaffe AE, Gao Y, Deep-Soboslay A, Tao R, Hyde TM, Weinberger DR, Kleinman JE. Mapping DNA methylation across development, genotype and schizophrenia in the human frontal cortex. Nat Neurosci. 2016 Jan;19(1):40-7. doi: 10.1038/nn.4181. Epub 2015 Nov 30.
Results Reference
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PubMed Identifier
27869829
Citation
Marshall CR, Howrigan DP, Merico D, Thiruvahindrapuram B, Wu W, Greer DS, Antaki D, Shetty A, Holmans PA, Pinto D, Gujral M, Brandler WM, Malhotra D, Wang Z, Fajarado KVF, Maile MS, Ripke S, Agartz I, Albus M, Alexander M, Amin F, Atkins J, Bacanu SA, Belliveau RA Jr, Bergen SE, Bertalan M, Bevilacqua E, Bigdeli TB, Black DW, Bruggeman R, Buccola NG, Buckner RL, Bulik-Sullivan B, Byerley W, Cahn W, Cai G, Cairns MJ, Campion D, Cantor RM, Carr VJ, Carrera N, Catts SV, Chambert KD, Cheng W, Cloninger CR, Cohen D, Cormican P, Craddock N, Crespo-Facorro B, Crowley JJ, Curtis D, Davidson M, Davis KL, Degenhardt F, Del Favero J, DeLisi LE, Dikeos D, Dinan T, Djurovic S, Donohoe G, Drapeau E, Duan J, Dudbridge F, Eichhammer P, Eriksson J, Escott-Price V, Essioux L, Fanous AH, Farh KH, Farrell MS, Frank J, Franke L, Freedman R, Freimer NB, Friedman JI, Forstner AJ, Fromer M, Genovese G, Georgieva L, Gershon ES, Giegling I, Giusti-Rodriguez P, Godard S, Goldstein JI, Gratten J, de Haan L, Hamshere ML, Hansen M, Hansen T, Haroutunian V, Hartmann AM, Henskens FA, Herms S, Hirschhorn JN, Hoffmann P, Hofman A, Huang H, Ikeda M, Joa I, Kahler AK, Kahn RS, Kalaydjieva L, Karjalainen J, Kavanagh D, Keller MC, Kelly BJ, Kennedy JL, Kim Y, Knowles JA, Konte B, Laurent C, Lee P, Lee SH, Legge SE, Lerer B, Levy DL, Liang KY, Lieberman J, Lonnqvist J, Loughland CM, Magnusson PKE, Maher BS, Maier W, Mallet J, Mattheisen M, Mattingsdal M, McCarley RW, McDonald C, McIntosh AM, Meier S, Meijer CJ, Melle I, Mesholam-Gately RI, Metspalu A, Michie PT, Milani L, Milanova V, Mokrab Y, Morris DW, Muller-Myhsok B, Murphy KC, Murray RM, Myin-Germeys I, Nenadic I, Nertney DA, Nestadt G, Nicodemus KK, Nisenbaum L, Nordin A, O'Callaghan E, O'Dushlaine C, Oh SY, Olincy A, Olsen L, O'Neill FA, Van Os J, Pantelis C, Papadimitriou GN, Parkhomenko E, Pato MT, Paunio T; Psychosis Endophenotypes International Consortium; Perkins DO, Pers TH, Pietilainen O, Pimm J, Pocklington AJ, Powell J, Price A, Pulver AE, Purcell SM, Quested D, Rasmussen HB, Reichenberg A, Reimers MA, Richards AL, Roffman JL, Roussos P, Ruderfer DM, Salomaa V, Sanders AR, Savitz A, Schall U, Schulze TG, Schwab SG, Scolnick EM, Scott RJ, Seidman LJ, Shi J, Silverman JM, Smoller JW, Soderman E, Spencer CCA, Stahl EA, Strengman E, Strohmaier J, Stroup TS, Suvisaari J, Svrakic DM, Szatkiewicz JP, Thirumalai S, Tooney PA, Veijola J, Visscher PM, Waddington J, Walsh D, Webb BT, Weiser M, Wildenauer DB, Williams NM, Williams S, Witt SH, Wolen AR, Wormley BK, Wray NR, Wu JQ, Zai CC, Adolfsson R, Andreassen OA, Blackwood DHR, Bramon E, Buxbaum JD, Cichon S, Collier DA, Corvin A, Daly MJ, Darvasi A, Domenici E, Esko T, Gejman PV, Gill M, Gurling H, Hultman CM, Iwata N, Jablensky AV, Jonsson EG, Kendler KS, Kirov G, Knight J, Levinson DF, Li QS, McCarroll SA, McQuillin A, Moran JL, Mowry BJ, Nothen MM, Ophoff RA, Owen MJ, Palotie A, Pato CN, Petryshen TL, Posthuma D, Rietschel M, Riley BP, Rujescu D, Sklar P, St Clair D, Walters JTR, Werge T, Sullivan PF, O'Donovan MC, Scherer SW, Neale BM, Sebat J; CNV and Schizophrenia Working Groups of the Psychiatric Genomics Consortium. Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects. Nat Genet. 2017 Jan;49(1):27-35. doi: 10.1038/ng.3725. Epub 2016 Nov 21. Erratum In: Nat Genet. 2017 Mar 30;49(4):651. Nat Genet. 2017 Sep 27;49(10 ):1558.
Results Reference
result

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Identification of Multi-modal Bio-markers for Early Diagnosis and Treatment Prediction in Schizophrenia Individuals

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