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

Official title

A New Intervention for Implementation of Pharmacogenetics in Psychiatry

Overview

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.

Detailed description

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.

Interventions

• Other 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

Primary outcome measures

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

Secondary outcome measures (10)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Germany · 2 centers

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

Netherlands · 2 centers

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

United States · 1 center

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

Romania · 1 center

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

Serbia · 1 center

• University of Belgrade, Faculty of Pharmacy — Belgrade

Spain · 1 center

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

United Kingdom · 1 center

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

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗