Prescribing the Right Agent for Depression in Adults (PRADA): a Double-blind, Randomised Controlled Trial Using a Web-based Multi-modal Clinical Decision Support System and Genetic Information to Personalise Antidepressant Treatment in Diverse Clinical Settings Across the Globe
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 2,142
- 试验地点
- 3
- 主要终点
- All-cause treatment discontinuation
研究概览
简要总结
Depression is a common mental health problem affecting almost 300 million people worldwide. Antidepressants are recommended as one of the first line treatments for people with moderate-to-severe symptoms of depression. In our recent trial, PETRUSHKA, on the acute treatment of depression, we demonstrated that the PETRUSHKA Tool, an evidence-based shared decision support system to personalise antidepressant treatment, in comparison with usual care reduced by almost 40% the number of participants stopping their antidepressant early, also improving their depression and anxiety symptoms. To identify the best treatment for each individual, the PETRUSHKA Tool used clinical and demographic predictors. Pilot data show that genetic information can aid stratification of people experiencing depression and better target their treatment. Genetic data can be collected using low-cost DNA-sequencing technology in diverse clinical settings and low-resource environments. Hence, we hypothesised that individual-level pharmacogenomic information can further personalise antidepressant treatment. In this project called PRADA ("Prescribing the Right Agent for Depression in Adults"), we will develop and test in a global trial across Ethiopia, Pakistan and the UK, an evidence-based multimodal web-tool to help participants and clinicians choose the best pharmacological treatment for depression jointly, based on participant preferences and their individual clinical, demographic, cultural, and also genetic profile (PRADA Tool). We will compare the new tool with the PETRUSHKA Tool in a blind fashion, measuring adherence to antidepressant treatment, clinical response and quality of life over a 12-month follow-up.
详细描述
Major depressive disorder (MDD) is characterised by substantial heterogeneity in treatment response and tolerability. Although antidepressants are recommended as first-line treatment for moderate-to-severe depression, in routine care the selection of a specific antidepressant remains largely empirical.
As a result, many patients discontinue treatment prematurely due to lack of efficacy, or the presence of intolerable side effects. This limits the overall effectiveness of pharmacological interventions.
Our previous trial PETRUSHKA, an international, multicentre randomised controlled trial (RCT), addressed this challenge by developing and evaluating a web-based clinical decision-support system that integrated clinical and demographic predictors with participant preferences to personalise antidepressant selection and treatment. We demonstrated that antidepressant treatment can be optimised for individuals by using socio-demographic and clinical predictors, and patient preferences.
Recent studies have shown the beneficial role of pharmacogenomics to improve antidepressant response and reduce adverse effects in patients with MDD. In 2023, the Clinical Pharmacogenetics Implementation Consortium provided updated guidelines for choice and dosage of SSRIs and SNRIs based on genotypes at CYP2D6, CYP2C19, and CYP2B6 variants. Notably, pharmacogenetic variants have been studied extensively across global populations, in which they have similar influences but different frequencies between ancestry groups. Polygenic scores (PGS), while not diagnostic per se, can also contribute useful information about risk. Advanced but economical DNA sequencing technologies now exist, suitable for use in low resource environments, returning results in as little as 48 hours. Hence, pharmacogenomic variants and PGS can provide timely individual-level information, especially about adverse effects and genetic vulnerability for depression, that can be used to further personalise treatments and empower patients in the management of their symptoms . Moreover, genetic data could help identify patient subgroups with specific molecular characteristics associated with clinical features, that can also inform animal model studies and ultimately support drug discovery in neuroscience.
The PRADA trial builds directly on the PETRUSHKA framework by evaluating an enhanced, multimodal clinical decision-support system that incorporates also pharmacogenomic information (the PRADA Tool), compared to a system based only on clinical and demographic factors and patient preferences (the PETRUSHKA Tool). The trial is aimed to determine whether the PRADA tool can further improve personalisation of antidepressant treatment, improving its acceptability and clinical outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18-74 years inclusive;
- •Willing and able to give informed consent for participation in the trial;
- •Clinical primary diagnosis of major depressive episode, for which an antidepressant is clinically indicated;
- •PHQ-9 score of at least 10;
- •Willing and able to start antidepressant treatment as monotherapy;
- •Able to understand and answer self-administered questionnaires in their local language.
排除标准
- •Taken an antidepressant in the preceding 4 weeks at a therapeutic dose;
- •Current or historical diagnosis (lifetime) of ADHD, bipolar disorder, dementia, mania/hypomania, psychosis/schizophrenia
- •Current or historical diagnosis (within 10 years) of any eating disorders, PTSD, OCD or alcohol/substance use disorder
- •Treatment Resistant Depression (i.e., having tried 2 or more antidepressants for the same depressive episode at adequate dose and time);
- •Known diagnosis of arrhythmias (including Q-T prolongation, heart block), recent myocardial infarction (within 5 years), difficult-to-treat epilepsy, acute porphyrias;
- •Requires urgent mental care or admission (including suicidal intent/plans);
- •Concurrently enrolled in another investigational medicinal product (IMP) trial that, in the opinion of the investigator, is likely to interfere with the PRADA trial or an interventional trial about depression;
- •Pregnant, planning pregnancy or lactating (self-reported);
- •Unable to give blood sample for genetic analysis.
研究组 & 干预措施
PRADA Tool
A web-based clinical decision-support system for participants and clinicians to enable personalised antidepressant treatment decision-making, using clinical and demographic predictors, pharmacogenomic information and individual preferences about adverse events.
At week 8, participants who consent to the optional Polygenic Score (PGS) sub-study will be randomised to receive either the Polygenic Score (PGS) material alone, or Polygenic Score (PGS) material with psychiatric genetic counselling (1:1, factorial)
干预措施: PRADA Tool (Other)
PETRUSHKA Tool
A web-based clinical decision-support system to enable personalised antidepressant treatment decision-making, using clinical and demographic predictors, and individual preferences about adverse events, but not pharmacogenomic information.
At week 8, participants who consent to the optional Polygenic Score (PGS) sub-study will be randomised to receive either the Polygenic Score (PGS) material alone, or Polygenic Score (PGS) material with psychiatric genetic counselling (1:1, factorial)
干预措施: PETRUSHKA Tool (Other)
结局指标
主要结局
All-cause treatment discontinuation
时间窗: Baseline to week 8
To determine whether using the PRADA Tool to "personalise" antidepressant treatment, results in an increased proportion of participants continuing the allocated treatment, compared to the PETRUSHKA Tool.
次要结局
未报告次要终点