A Study of Antipsychotics in Individuals at Clinical High-risk for Psychosis (the SHARP-2 Study)

Real-world Effectiveness and Safety of Antipsychotics in Individuals at Clinical High-risk for Psychosis: Study Protocol for a Prospective Observational Study (SHARP-2)

The current study will improve knowledge on the effectiveness and safety of the use of antipsychotics at the prodromal phase and on factors influencing the outcome, and will eventually facilitate optimisation of individualised interventions for psychosis prevention and treatment.

Study Overview

• Status: Unknown
• Conditions: Clinical High-risk
• Intervention / Treatment: Other: routine clinical treatment

Detailed Description

Help-seeking first-visit participants will be consecutively recruited. Every participant meeting the inclusion criteria will be fully informed of the study and asked to sign the written informed consent before enrolment.

Two senior nurses that will conduct the initial screenings were employed to collect all diagnostic and medication information from medical records on every follow-up visit. The four psychiatrists are qualified and well-trained and will conduct the SIPS/SOPS interview at baseline and follow-up.

The investigators will systematically record medication information. A model will be established to correlate antipsychotics with clinical and functional outcomes and demonstrate whether antipsychotics are useful and safe for preventing CHR individuals from converting to psychosis.

Based on experience from the sampling process in the SHARP-1 project, the investigators will recruit 600 participants at CHR. Considering a dropout rate of 20%, 510 cases of CHR will be followed up. According to the sample size calculation formula in superiority clinical trials of new drugs, the sample size of 600 cases is adequate for the demonstration of the effectiveness and safety of antipsychotics in CHR subjects.

• Study Type: Observational
• Enrollment (Anticipated): 600

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 45 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Help-seeking first-visit participants will be consecutively recruited from the Shanghai Psychotherapy and Psychological Counselling Centre at the Shanghai Mental Health Centre. They will be screened for eligibility by their clinicians.

Description

Inclusion Criteria:

• be aged 14 to 45-year-old
• have had at least 6-years of primary education
• be drug-naïve
• be understanding the survey, be willing to enrol in the study and sign the informed consent
• Through the Structured Interview for Prodromal Syndromes/Scale of Prodromal Symptoms (SIPS/SOPS), the participants should meet the Criteria of Prodromal Syndrome. Participants should fulfil at least one of the prodromal syndrome criteria: (1) brief intermittent psychotic syndrome, (2) attenuated positive symptom syndrome, or (3) genetic risk and deterioration syndrome

Exclusion Criteria:

• Through the Mini-International Neuropsychiatric Interview (MINI), Axis I mental disorders such as schizophrenia, affective disorders, and anxiety spectrum disorders will be excluded
• Acute or chronic renal failure; liver cirrhosis or active liver diseases
• Abnormal laboratory tests results judged by the researchers to be clinically significant and considered to affect the efficacy of the test drugs or the safety of the subjects
• Severe or unstable physical diseases, including: neurological disorders (delirium, dementia, stroke, epilepsy, migraine, etc.), congestive heart failure, angina pectoris, myocardial infarction, arrhythmia, hypertension (including untreated or uncontrolled hypertension), malignant tumours, immune compromise, and blood glucose above 12 mmol/L
• Alcohol abuse within 30 days, or alcohol or drug dependence within 6 months before the trial
• Pregnant or lactating women, or women in childbearing age who are positive in urine human chorionic gonadotropin test, or men and women who do not take effective contraceptive measures or plan for pregnancy within 3 months after the initiation of the trial
• Stroke within the last month
• Participating in any clinical trial within 30 days before the baseline
• Other situations judged by the investigators not to be suitable for the clinical trial

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SHARP-2; ShangHai At Risk for Psychosis-Phase 2	Other: routine clinical treatment; Participants will be informed that this is not a treatment study and it involves naturalistic follow-up without any extra intervention. They will otherwise follow the routine clinical treatment procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conversion to psychosis	It will be determined using the criteria for the Presence of Psychotic Symptoms from SIPS. Specifically, the conversion will be defined by the presence of level 6 positive symptoms (the rating "6" refers to severe and psychotic symptoms) identified as either dangerous, disorganised, or occurring at least one hour a day on average, over four days a week for at least 16 hours.	4 weeks
Poor function	It will be determined by GAF score. Specifically, poor function outcome is defined as the GAF score of less than 60 at the follow-up point.	4 weeks

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Collaborators: National Natural Science Foundation of China; Ministry of Science and Technology of the People´s Republic of China; Shanghai Jiao Tong University School of Medicine; Shanghai Municipal Science and Technology Commission
• Investigators: Principal Investigator: TianHong Zhang, Doctor, Shanghai Mental Health Center

Publications and helpful links

General Publications

• Fusar-Poli P, Borgwardt S, Bechdolf A, Addington J, Riecher-Rossler A, Schultze-Lutter F, Keshavan M, Wood S, Ruhrmann S, Seidman LJ, Valmaggia L, Cannon T, Velthorst E, De Haan L, Cornblatt B, Bonoldi I, Birchwood M, McGlashan T, Carpenter W, McGorry P, Klosterkotter J, McGuire P, Yung A. The psychosis high-risk state: a comprehensive state-of-the-art review. JAMA Psychiatry. 2013 Jan;70(1):107-20. doi: 10.1001/jamapsychiatry.2013.269.
• McGorry PD, Yung AR, Phillips LJ, Yuen HP, Francey S, Cosgrave EM, Germano D, Bravin J, McDonald T, Blair A, Adlard S, Jackson H. Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms. Arch Gen Psychiatry. 2002 Oct;59(10):921-8. doi: 10.1001/archpsyc.59.10.921.
• Nelson B, Yuen HP, Wood SJ, Lin A, Spiliotacopoulos D, Bruxner A, Broussard C, Simmons M, Foley DL, Brewer WJ, Francey SM, Amminger GP, Thompson A, McGorry PD, Yung AR. Long-term follow-up of a group at ultra high risk ("prodromal") for psychosis: the PACE 400 study. JAMA Psychiatry. 2013 Aug;70(8):793-802. doi: 10.1001/jamapsychiatry.2013.1270. Erratum In: JAMA Psychiatry. 2013 Oct;70(10):1008.
• Lindstrom E, Bingefors K. Patient compliance with drug therapy in schizophrenia. Economic and clinical issues. Pharmacoeconomics. 2000 Aug;18(2):106-24. doi: 10.2165/00019053-200018020-00002.
• Crumlish N, Whitty P, Clarke M, Browne S, Kamali M, Gervin M, McTigue O, Kinsella A, Waddington JL, Larkin C, O'Callaghan E. Beyond the critical period: longitudinal study of 8-year outcome in first-episode non-affective psychosis. Br J Psychiatry. 2009 Jan;194(1):18-24. doi: 10.1192/bjp.bp.107.048942.
• Zhang T, Xu L, Tang Y, Cui H, Wei Y, Wang J, Tang X, Li C, Wang J. Duration of untreated prodromal symptoms in a Chinese sample at a high risk for psychosis: demographic, clinical, and outcome. Psychol Med. 2018 Jun;48(8):1274-1281. doi: 10.1017/S0033291717002707. Epub 2017 Nov 27.
• Zhang T, Xu L, Tang Y, Cui H, Tang X, Wei Y, Wang Y, Hu Q, Qian Z, Liu X, Li C, Wang J. Relationship between duration of untreated prodromal symptoms and symptomatic and functional recovery. Eur Arch Psychiatry Clin Neurosci. 2019 Dec;269(8):871-877. doi: 10.1007/s00406-018-0917-z. Epub 2018 Jun 25.
• Zhang T, Cui H, Wei Y, Tang Y, Xu L, Tang X, Zhu Y, Jiang L, Zhang B, Qian Z, Chow A, Liu X, Li C, Xiao Z, Wang J. Progressive decline of cognition during the conversion from prodrome to psychosis with a characteristic pattern of the theory of mind compensated by neurocognition. Schizophr Res. 2018 May;195:554-559. doi: 10.1016/j.schres.2017.08.020. Epub 2017 Aug 18.
• Zhang T, Cui H, Tang Y, Xu L, Li H, Wei Y, Liu X, Chow A, Li C, Jiang K, Xiao Z, Wang J. Correlation of social cognition and neurocognition on psychotic outcome: a naturalistic follow-up study of subjects with attenuated psychosis syndrome. Sci Rep. 2016 Oct 10;6:35017. doi: 10.1038/srep35017.
• Collin G, Seidman LJ, Keshavan MS, Stone WS, Qi Z, Zhang T, Tang Y, Li H, Anteraper SA, Niznikiewicz MA, McCarley RW, Shenton ME, Wang J, Whitfield-Gabrieli S. Functional connectome organization predicts conversion to psychosis in clinical high-risk youth from the SHARP program. Mol Psychiatry. 2020 Oct;25(10):2431-2440. doi: 10.1038/s41380-018-0288-x. Epub 2018 Nov 8.
• Shakory S, Watts JJ, Hafizi S, Da Silva T, Khan S, Kiang M, Bagby RM, Chavez S, Mizrahi R. Hippocampal glutamate metabolites and glial activation in clinical high risk and first episode psychosis. Neuropsychopharmacology. 2018 Oct;43(11):2249-2255. doi: 10.1038/s41386-018-0163-0. Epub 2018 Jul 28.
• Rauchensteiner S, Kawohl W, Ozgurdal S, Littmann E, Gudlowski Y, Witthaus H, Heinz A, Juckel G. Test-performance after cognitive training in persons at risk mental state of schizophrenia and patients with schizophrenia. Psychiatry Res. 2011 Feb 28;185(3):334-9. doi: 10.1016/j.psychres.2009.09.003. Epub 2010 May 21.
• Amminger GP, Schafer MR, Papageorgiou K, Klier CM, Cotton SM, Harrigan SM, Mackinnon A, McGorry PD, Berger GE. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry. 2010 Feb;67(2):146-54. doi: 10.1001/archgenpsychiatry.2009.192.
• McGorry PD, Nelson B, Markulev C, Yuen HP, Schafer MR, Mossaheb N, Schlogelhofer M, Smesny S, Hickie IB, Berger GE, Chen EY, de Haan L, Nieman DH, Nordentoft M, Riecher-Rossler A, Verma S, Thompson A, Yung AR, Amminger GP. Effect of omega-3 Polyunsaturated Fatty Acids in Young People at Ultrahigh Risk for Psychotic Disorders: The NEURAPRO Randomized Clinical Trial. JAMA Psychiatry. 2017 Jan 1;74(1):19-27. doi: 10.1001/jamapsychiatry.2016.2902.
• Zeng J, Raballo A, Gan R, Wu G, Wei Y, Xu L, Tang X, Hu Y, Tang Y, Chen T, Li C, Wang J, Zhang T. Antipsychotic Exposure in Clinical High Risk of Psychosis: Empirical Insights From a Large Cohort Study. J Clin Psychiatry. 2022 Mar 21;83(3):21m14092. doi: 10.4088/JCP.21m14092.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 29, 2019
• Primary Completion (ANTICIPATED): December 1, 2022
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: July 4, 2019
• First Submitted That Met QC Criteria: July 4, 2019
• First Posted (ACTUAL): July 8, 2019

Study Record Updates

• Last Update Posted (ACTUAL): October 22, 2020
• Last Update Submitted That Met QC Criteria: October 19, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Psychotic Disorders
• Other Study ID Numbers: CRC2018ZD04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No