Evaluating Pharmacogenomics-Based Pharmacotherapy in Real-World Settings for Schizophrenia

Официальное название

A Precision Medication Guidance Model for Schizophrenia Based on Pharmacogenomics and Physiologically Based Pharmacokinetics: a Real-World Observational Study

Обзор

An 8-week, rater-blinded, real-world observational study to investigate the benefits of pharmacogenetics-based pharmacotherapy in patients suffering from schizophrenia.

Подробное описание

This study, conducted at the Shanghai Mental Health Center, aims to compare changes in treatment efficacy and the frequency and severity of adverse reactions in patients with schizophrenia who have experienced treatment failure, before and after implementing a pharmacogenomics-based precision medication guidance strategy. The research is set in real-world conditions, without a predetermined treatment regimen for participants; instead, medication optimization is guided by pharmacogenomic testing results. Following the receipt of precision medication recommendations for each participant, the study physicians optimize the treatment regimen based on these recommendations and their clinical expertise. Optimization may involve adjusting the dose of current medications (if the existing regimen is largely suitable), switching medications (in cases of inappropriate treatment), or modifying the dose or replacing one of the combined medications (to manage drug-drug interactions). The rationality of the medication regimen will be assessed at the end of weeks 4 and 8, with additional recommendations provided as needed. Treatment effectiveness and safety will be evaluated during follow-up visits at these intervals. A total of 400 patients are planned to be included in the study.

Первичные конечные точки

• Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Total Score at Week 4 and Week 8 [Срок оценки: 4 weeks and 8 weeks]

Вторичные конечные точки (7)

• Change in the Calgary Depression Scale for Schizophrenia (CDSS) [Срок оценки: 4 weeks and 8 weeks]
• Change in the Clinical Global Impression of Severity (CGI-S) [Срок оценки: 4 weeks and 8 weeks]
• Clinical Laboratory Tests [Срок оценки: 4 weeks and 8 weeks]
• Safety Assessment by the Treatment Emergent Symptom Scale (TESS) score [Срок оценки: 4 weeks and 8 weeks]
• Safety Assessment by Barnes Akathisia Rating Scale(BARS) [Срок оценки: 4 weeks and 8 weeks]
• Safety Assessment by Simpson-Angus Scale(SAS) [Срок оценки: 4 weeks and 8 weeks]
• Safety Assessment by Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score [Срок оценки: 4 weeks and 8 weeks]

Критерии участия

Критерии включения

• Suffer from schizophrenia (as assessed in agreement with ICD-11 criteria).
• Age between ≥18 and <65 years.
• Currently receiving inpatient or outpatient psychiatric treatment.
• Experienced any of the following suboptimal treatment conditions while receiving antipsychotic medication within the therapeutic dosage range:

• Standard antipsychotic treatment for more than 2 weeks with the occurrence of drug-induced adverse effects requiring dose adjustment or a switch of medication.
• Antipsychotic treatment within the therapeutic dosage range for more than 4 weeks, with the presence of at least two items of the Positive and Negative Syndrome Scale (PANSS) (P1, P2, P3, N1, N4, N6, G5, and G9) score ≥4, or a total PANSS score >70, or a CGI-S score ≥4.
• Other situations where a change in medication is deemed necessary, as assessed by senior clinical physicians.
• Understand the study requirements and provide written informed consent to participate; a signed and dated informed consent form (ICF) will be obtained from each patient before participation in the study.

Критерии исключения

• Presence of organic brain disease or a severe and/or unstable physical condition.
• Substance abuse or dependence within the past 6 months or currently.
• Presence of elevated levels of agitation, impulsivity, or risk of self-injury or suicide.
• Pregnant or breastfeeding women.
• The presence of any other conditions that may render the individual ineligible for participation in this clinical trial.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Китай · 1 центр

• Shanghai Mental Health Center — Шанхай

Публикации

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• Lindenmayer JP, Citrome L, Khan A, Kaushik S, Kaushik S. A randomized, double-blind, parallel-group, fixed-dose, clinical trial of quetiapine at 600 versus 1200 mg/d for patients with treatment-resistant schizophrenia or schizoaffective disorder. J Clin Psychopharmacol. 2011 Apr;31(2):160-8. doi: 10.1097/JCP.0b013e31820f4fe0. PMID 21346616
• Wojtyniak JG, Selzer D, Schwab M, Lehr T. Physiologically Based Precision Dosing Approach for Drug-Drug-Gene Interactions: A Simvastatin Network Analysis. Clin Pharmacol Ther. 2021 Jan;109(1):201-211. doi: 10.1002/cpt.2111. Epub 2020 Dec 6. PMID 33280091
• Hahn M, Roll SC. The Influence of Pharmacogenetics on the Clinical Relevance of Pharmacokinetic Drug-Drug Interactions: Drug-Gene, Drug-Gene-Gene and Drug-Drug-Gene Interactions. Pharmaceuticals (Basel). 2021 May 20;14(5):487. doi: 10.3390/ph14050487. PMID 34065361
• Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK; Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005 Sep 22;353(12):1209-23. doi: 10.1056/NEJMoa051688. Epub 2005 Sep 19. PMID 16172203

Идентификаторы

NCT: NCT06700967 · CRC2021ZD02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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