Clinical Study Evaluating Pharmacogenomics-informed Pharmacotherapy Versus Dosing as Usual in Psychiatric Disorders

Официальное название

A New Intervention for Implementation of Pharmacogenetics in Psychiatry

Обзор

A 24-week, patient- and rater-blinded, two-arm, parallel-group controlled, and multi-centre randomized clinical trial (RCT) to establish the benefits of pharmacogenetics-informed pharmacotherapy versus dosing as usual (DAU) in psychiatric patients suffering from mood, anxiety, or psychotic disorders.

Подробное описание

Effective pharmacotherapeutic treatments for mental disorders are available, but their effectiveness is limited by low compliance due to frequent side effects. This is partly due to patient heterogeneity in the genes encoding for drug-metabolising enzymes. Pharmacogenetic testing allows the assessment of person-specific genetic factors that are thought to predict clinical response and side effects. Recent studies have suggested that genotyping genes encoding drug-metabolizing enzymes may improve treatment efficacy and tolerability, potentially benefitting millions of patients.

PSY-PGx is the first initiative to propose a large-scale non-industry sponsored clinical study that aims to demonstrate the clinical benefits and potential of the implementation of pharmacogenetics for psychiatric patients in existing medical settings.

This is an international 24-week, patient- and rater-blinded, two-arm, parallel-group controlled, and multi-centre randomized clinical trial (RCT) to establish the benefits of pharmacogenetics-informed pharmacotherapy versus dosing as usual (DAU) in psychiatric patients suffering from mood, anxiety, or psychotic disorders.

Вмешательства

• Другое Personalised medication advice based on pharmacogenetic testing
  Pharmacogenetic genotyping provides personalised medication advice on dosage and choice of currently available and legally approved medication based on the patient's pharmacogenetic profile

Первичные конечные точки

• Patient recovery, as assessed using the Patient Recovery Assessment scale - Domains and Stages (RAS-DS). [Срок оценки: 24 weeks]

Вторичные конечные точки (10)

• Response Mood Disorder, defined as a 50% point reduction in the following scale: [Срок оценки: 24 weeks]
• Response Anxiety Disorder, defined as a 50% point reduction in the following scale: [Срок оценки: 24 weeks]
• Response Psychotic Disorder, defined as a 50% point reduction in the following scale: [Срок оценки: 24 weeks]
• Symptomatic Remission Mood Disorder, defined as: [Срок оценки: 24 weeks]
• Symptomatic Remission Anxiety Disorder, defined as: [Срок оценки: 24 weeks]
• Symptomatic Remission Psychotic Disorder, defined as: [Срок оценки: 24 weeks]
• Burden of side effects, as measured by: [Срок оценки: 24 weeks]
• Side effects, as measured by: [Срок оценки: 24 weeks]
• General wellbeing, as measured by: [Срок оценки: 24 weeks]
• Psychosocial functioning, as measured by: [Срок оценки: 24 weeks]

Критерии участия

Критерии включения

• Suffer from a depressive episode (major depressive disorder and bipolar disorder (currently depressive episode)) (as assessed by the MINI International Neuropsychiatric Interview (M.I.N.I.) in agreement with Diagnostic and Statistical Manual (DSM-5 criteria) of at least moderate severity (assessed using the Structured Interview Guide for the Hamilton Depression Scale (SIGH-D) with a score of 14 or higher) and/or suffer from an anxiety disorder (panic disorder, generalised anxiety disorder) (as assessed by the M.I.N.I. in agreement with DSM-5 criteria) of at least moderate severity (assessed using the Structured Interview Guide for the Hamilton Anxiety Scale (SIGH- A) with a score of 18 or higher) and/or suffer from a psychotic disorder (schizophrenia and schizoaffective disorder) (as assessed by the M.I.N.I. in agreement with DSM-5 criteria) of at least moderate severity (assessed using the Positive and Negative Symptom Scale (PANSS) with a score of 75 or higher).
• Have had an inadequate response to at least 1 psychotropic treatment during their life-time. Inadequate response is defined as insufficient efficacy of a psychotropic treatment when dosed high enough and maintained long enough, or discontinuation of a psychotropic treatment due to AEs or intolerability.
• Are about to switch (or have switched within the last 2 weeks prior to first contact with an investigator) to sertraline or escitalopram (for patients with mood or anxiety disorders), or to aripiprazole or risperidone (for patients with psychotic disorders) due to an inadequate response to or intolerance of the current/ previous medication.
• Currently receiving inpatient or outpatient psychiatric treatment.
• Be able to understand the requirements of the study and provide written informed consent to participate in this study; a signed and dated informed consent form (ICF) will be obtained from each patient before participation in the study.
• To give written consent to the use and disclosure of clinical data from their medical records for the purpose of this study.
• Age between ≥16 and <70 years.
• Ownership of a mobile phone (Android or iOS operation system) for passive monitoring.

Критерии исключения

• Patients with a history of prior pharmacogenomic testing
• Patients with no prior use of psychotropic medication (medication-naïve patients)
• Severe somatic comorbidities as reported in the subject's medical history or based on clinical chemistry/electrocardiography (ECG) results up to six months ago. If any of these comorbidities is detected on the basis of physical examination and/or clinical chemistry and/or ECG at the screening visit, participation is not possible.

• Liver disease defined as follows: Alanine-Aminotransferase (ALAT) >70u/L
• Renal disease: Estimated glomerular filtration rate (eGFR) < 60ml/min/1.73m2
• Diabetes: Blood glucose > 11.1 mmol/L or twice a fasting glucose > 7.0 mmol/L
• Cardiac disease: prolonged QT-interval.
• Alcohol and/or substance abuse and/or dependence (except nicotine)
• Polypharmacy defined as the routine use of five or more medications including over- the-counter, prescription and/or traditional and complementary medicines used by a patient (WHO 2019).
• Inability to use the mobile phone application
• Pregnant or breastfeeding women

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Германия · 2 центра

• University Hospital Bonn, Department of Psychiatry and Psychotherapy — Bonn
• Ludwig-Maximilian University, University Hospital, Institute of Psychiatric Phenomics and — München

Нидерланды · 2 центра

• Parnassia Psychiatric Institute, Department of Psychiatry — Amsterdam
• Maastricht University, Department of Psychiatry and Neuropsychology — Maastricht

США · 1 центр

• SUNY Upstate Medical University, Department of Psychiatry and Behavioural Sciences — Syracuse

Румыния · 1 центр

• Babeş-Bolyai University, Department of Clinical Psychology and Psychotherapy — Cluj-Napoca

Сербия · 1 центр

• University of Belgrade, Faculty of Pharmacy — Belgrade

Испания · 1 центр

• Fundació Clínic per a la Recerca Biomèdica, Department of Psychiatry and Psychology, Ho — Barcelona

Великобритания · 1 центр

• King's College, Institute of Psychiatry, Psychology & Neuroscience — London

Идентификаторы

NCT: NCT05656469 · NL79649.068.21 · 2023-509680-25-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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