Validation of a Composite Medical Device Using a Blood Biomarker-based Algorithm and MDQ for the Diagnosis of Bipolar Disorder in Patients With a Characterized Depressive Episode in Primary Care
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 623
- 试验地点
- 1
- 主要终点
- Sensitivity and specificity of the composite medical device, using the full clinical evaluation as a reference
研究概览
简要总结
The goal of this interventional clinical trial is to assess the diagnostic performance of a composite diagnostic medical devise based on blood-based in vitro diagnostic device and Mood Disorder Questionnaire (MDQ) in identifying bipolar disorder among adult patients presenting with a current major depressive episode in primary care. The study will compare the results of the medical device diagnostic test to those of standardized psychiatric clinical evaluation, to evaluate its sensitivity, specificity, and overall clinical utility.
The main research questions are :
- Can the investigational medical device accurately distinguish bipolar disorder from unipolar depression ?
- How does its diagnostic accuracy compare with validated psychiatric questionnaires commonly used in clinical practice ?
Participants will :
- Provide a blood sample for biomarker analysis using the investigational diagnostic device.
- Complete a few validated psychiatric assessment tools (e.g., MDQ, MINI).
- Share sociodemographic and clinical data relevant to psychiatric evaluation.
详细描述
Introduction
Bipolar disorder (BD) is a chronic and disabling condition affecting between 1% to 2.5% of the population, corresponding to approximately 650,000 to 1,650,000 individuals in France. Onset typically occurs between the ages of 15 and 25, with symptoms persisting throughout life. Bipolar disorder ranks as the sixth leading cause of disability globally, according to the World Health Organization (WHO). Additionally, individuals with bipolar disorder face a reduced life expectancy of around 10 years compared with the general population. This increased mortality is partly attributed to suicide, as approximately 20% of untreated BD patients die by suicide. In addition, BD is associated with a high prevalence of comorbidities such as alcohol or substance use disorders, diabetes, dyslipidaemia, which significantly heighten the risk of developing other diseases, notably cardiovascular pathologies. Risky behaviors, including impulsive spending, substance use, and unsafe sexual practices, further contribute to the functional impairments experienced by those with bipolar disorder. Clinically, bipolar disorder is characterized by alternating episodes of depression and mania or hypomania. While mania and hypomania are hallmark features of bipolar disorder, depressive episodes are more frequent and often serve as the initial clinical manifestation. This overlap with Major Depressive Disorder presents diagnostic challenges, particularly since patients often seek treatment during depressive phases, usually from general practitioners.
Current diagnostic approaches for bipolar disorder rely heavily on clinical assessment, necessitating detailed knowledge of mood disorders and extensive patient interviews-both of which are often impractical in primary care settings. Consequently, many bipolar disorder patients are misdiagnosed with major depressive disorder and receive inappropriate treatment with antidepressants, which can exacerbate the condition. Studies indicate that the prevalence of undiagnosed bipolar disorder in patients treated with antidepressants ranges around 10% in primary care to 16%-47% in psychiatric settings. In this context, the average diagnostic delay of bipolar disorder is 8 years in France. Early diagnosis and treatment could significantly improve the outcomes for bipolar disorder patients.
Self-administered tools such as the Mood Disorder Questionnaire (MDQ) offer potential solutions to improve bipolar disorder screening. The MDQ evaluates symptoms of mania or hypomania through a structured questionnaire divided into three sections: (1) assessment of 13 symptoms related to mania/hypomania, (2) evaluation of symptom temporality, and (3) determination of symptom impact on daily life. Despite its simplicity and utility, the MDQ has notable limitations, including low sensitivity (43%) and high specificity (95%), which restricts its standalone diagnostic reliability in primary care settings.
In this context, the development of an in vitro diagnostic test based on blood biomarkers, enabling differential diagnosis between bipolar disorder and major depressive disorder in patients with major depressive episode, represents a critical advancement. Recent research underscored the potential utility of biomarkers to complement clinical evaluations and enhance diagnostic accuracy. A predictive model was developed incorporating routinely measured blood-based biomarkers, such as eosinophil counts, prolactin levels, total cholesterol (TC), and low-density lipoprotein (LDL) cholesterol, to differentiate bipolar disorder from major depressive disorder. Their nomogram demonstrated robust discriminatory power with an area under the curve (AUC) of 0.858, highlighting the promise of biomarker-based diagnostics. Another notable development in this area is the Edit-B® test, which utilizes RNA editing markers and was introduced in France in 2024. However, this test has faced regulatory challenges, emphasizing the need of alternative diagnostic solutions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Cis man, cis woman, trans man, trans woman or non-binary,
- •Aged 18 to 65 years old,
- •Meets the DSM-5 criteria for the diagnosis of moderate to severe EDC and is eligible for antidepressant treatment.
- •Non-Inclusion Criteria :
- •Patients under guardianship or trusteeship,
- •Patients with schizophrenia according to DSM-5 criteria,
- •Patients who have received psychotropic treatment in the 5 days prior to inclusion (or 21 days for fluoxetine or aripiprazole), with the exception of benzodiazepines and hydroxyzine at the doses and in compliance with the indications of the Marketing Authorisations,
- •Patients with an unstable physiological state or a serious and symptomatic medical condition in the opinion of the investigator,
- •Pregnant or breast-feeding patients,
- •Patients with a known autoimmune disease, in particular Crohn's disease or thyroiditis, or any other pathology which could, in the opinion of the investigator, modify the blood concentration of immune biomarkers,
- •Patients unable to give informed consent to participate in the study or who cannot be given informed information,
- •Patients not covered by a social security scheme,
- •Patients participating in another interventional study on the day of inclusion,
- •Patients under court protection,
- •Patients vaccinated less than 30 days ago,
- •Patients with difficulties reading, understanding or speaking French.
排除标准
- •Participants will have the right to withdraw their consent at any time for any reason whatsoever without any prejudice to them,
- •The investigator may prematurely exclude a subject from the study, in agreement with the sponsor, if the subject presents one or more exclusion criteria,
- •Diagnosis of schizophrenia during follow-up or any other diagnosis that would lead to a change in the initial EDC diagnosis,
- •Any condition or situation which, in the opinion of the investigator, would be incompatible with the continuation of the study or which would lead to a bias in the management of the data.
研究组 & 干预措施
Diagnostic Evaluation Arm
Participants in this arm will undergo the full diagnostic procedure under investigation. This includes :
- A blood sample collected for analysis by the investigational in vitro diagnostic device targeting biomarkers associated with bipolar disorder,
- Completion of validated psychiatric questionnaires, including the Mood Disorder Questionnaire (MDQ), used as clinical reference standards,
- Collection of sociodemographic and clinical data relevant to the psychiatric profile. This arm does not involve any therapeutic intervention. The objective is to evaluate the diagnostic concordance between the blood test and psychiatric screening tools.
干预措施: Venous blood sample for measuring blood biomarkers related to bipolar disorder (Diagnostic Test)
Diagnostic Evaluation Arm
Participants in this arm will undergo the full diagnostic procedure under investigation. This includes :
- A blood sample collected for analysis by the investigational in vitro diagnostic device targeting biomarkers associated with bipolar disorder,
- Completion of validated psychiatric questionnaires, including the Mood Disorder Questionnaire (MDQ), used as clinical reference standards,
- Collection of sociodemographic and clinical data relevant to the psychiatric profile. This arm does not involve any therapeutic intervention. The objective is to evaluate the diagnostic concordance between the blood test and psychiatric screening tools.
干预措施: Standardized psychiatric assessment tools (Other)
结局指标
主要结局
Sensitivity and specificity of the composite medical device, using the full clinical evaluation as a reference
时间窗: Through study completion, an 8 weeks follow-up for each patient
To assess the sensitivity and specificity of a composite diagnostic device using a biomarker-based algorithm (IL-6, IL-10, IL-15, IL-27, CXCL10), combined with clinical data (age, depression severity via QIDS, psychotropic treatment), to identify bipolar disorder in primary care patients with a depressive episode. The algorithm, developed by the investigators, will be implemented in the eCRF and classify patients as bipolar, non-bipolar, or in a grey zone. The reference diagnosis will be established by an expert psychiatrist using the MINI interview and a full clinical evaluation, including medical history and patient records, following standardized procedures for optimal diagnostic accuracy.
次要结局
- Area under the curve(Through study completion, an 8 weeks follow-up for each patient)
- Negative predictive value(Through study completion, an 8 weeks follow-up for each patient)
- Positive predictive value(Through study completion, an 8 weeks follow-up for each patient)
- Occurence of hypomanic symptoms(From inclusion to the last visit at 7/9 weeks later)
- Improvement in depression according to the MADRS scale(From inclusion to the last visit at 7/9 weeks later)
- Improvement in depression according to the QIDS self-assessment questionnaire(From inclusion to the last visit at 7/9 weeks later)
- Improvement in depression according to the Patient Health Questionnaire (PHQ-9) self-assessment questionnaire(From inclusion to the last visit at 7/9 weeks later)
- Diagnosis of bipolar disorder(At the last visit between 7 and 9 weeks after inclusion)
- Inter-operator variability in the measurement of biomarkers of bipolar disorder(Through study completion, an 8 weeks follow-up for each patient)
- Inter-method variability in the measurement of biomarkers of bipolar disorder(Through study completion, an 8 weeks follow-up for each patient)
- Inter-site variability in the measurement of biomarkers of bipolar disorder(Through study completion, an 8 weeks follow-up for each patient)
- Acceptability of the composite medical device(Through study completion, an 8 weeks follow-up for each patient)
- Likert scale for the diagnosis of bipolar disorder in primary care(Through study completion, an 8 weeks follow-up for each patient)
- Assay of ASAT (Aspartate Aminotransferase)(Through study completion, an 8 weeks follow-up for each patient)
- Assay of ALAT (Alanine Aminotransferase)(Through study completion, an 8 weeks follow-up for each patient)
- Assay of Alkaline Phosphatase(Through study completion, an 8 weeks follow-up for each patient)
- Assay of GGT (Gamma-Glutamyl Transferase)(Through study completion, an 8 weeks follow-up for each patient)
- Assay of Lactate Dehydrogenase (LDH)(Through study completion, an 8 weeks follow-up for each patient)
- Assay of Total Bilirubin(Through study completion, an 8 weeks follow-up for each patient)
- Assay of Conjugated Bilirubin(Through study completion, an 8 weeks follow-up for each patient)
- Assay of Unconjugated Bilirubin(Through study completion, an 8 weeks follow-up for each patient)
- Assay of Uric Acid(Through study completion, an 8 weeks follow-up for each patient)
- Assay of Creatinine(Through study completion, an 8 weeks follow-up for each patient)
- Assay of Triglycerides(Through study completion, an 8 weeks follow-up for each patient)
- Assay of Total Cholesterol(Through study completion, an 8 weeks follow-up for each patient)
- Assay of HDL Cholesterol(Through study completion, an 8 weeks follow-up for each patient)
- Assay of LDL Cholesterol(Through study completion, an 8 weeks follow-up for each patient)
- Assay of Albumin(Through study completion, an 8 weeks follow-up for each patient)
- Assay of Urea(Through study completion, an 8 weeks follow-up for each patient)
- Assay of CRP (C-Reactive Protein)(Through study completion, an 8 weeks follow-up for each patient)
- Assay of Free Triiodothyronine (FT3)(Through study completion, an 8 weeks follow-up for each patient)
- Medico-economic impact of the composite medical device(Through study completion, an 8 weeks follow-up for each patient)