Study on Multidimensional Biomarkers of Depression and Individualized Therapy Based on Pharmacogenomic Technology
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 220
- 主要终点
- Title: 12-Week Response Rate Defined by HAMD-17 Score Reduction
研究概览
简要总结
Background: The clinical management of major depressive disorder (MDD) is hampered by the lack of objective biomarkers and high inter-individual variability in drug response, with conventional antidepressants achieving only a 50% response rate.
Objective and Design: This prospective, randomized, parallel-controlled trial aims to enroll 220 MDD patients, who will be allocated 1:1 to either a pharmacogenomics (PGx)-guided therapy group (treatment selection based on genetic testing) or a conventional treatment group (treatment as usual per guidelines), with a 12-week follow-up. Additionally, a matched healthy control cohort will be included for cross-sectional biomarker comparisons.
Intervention and Outcomes: Patients in the PGx group undergo buccal swab testing for key genetic polymorphisms (e.g., CYP2D6, CYP2C19) to inform antidepressant type and dosage. The primary outcome is the 12-week response rate (≥50% reduction in HAMD-17 score from baseline). Secondary outcomes include remission rate, incidence of adverse drug reactions, and medication adjustment frequency.
Exploratory Aims: Multidimensional baseline data-including resting-state fMRI (VMHC), peripheral blood biomarkers (inflammatory cytokines, thyroid function, BDNF), urinary metabolites, and gut microbiome-will be integrated to construct a predictive model for treatment efficacy and to identify novel MDD biomarkers.
Scientific Significance: This study seeks to validate the clinical utility of PGx-guided prescribing and to advance the shift from symptom-based diagnosis towards a biological-characteristic-based precision medicine framework for depression.
详细描述
- Study Design and Overall Framework This is a prospective, randomized, parallel-controlled, single-center clinical trial, conducted in accordance with the Declaration of Helsinki and Chinese ethical regulations. A total of 220 patients diagnosed with major depressive disorder (MDD) per DSM-5 criteria will be enrolled, along with 80-100 age-, sex-, and education-matched healthy controls (retrospective data from an anonymized health check-up database). Patient participants will be randomized 1:1 via block randomization (block size 4-6) into: (1) Pharmacogenomics (PGx)-guided therapy group; (2) Conventional treatment group (guideline- and experience-based). The follow-up duration is 12 weeks, with assessments scheduled at baseline, Week 4, Week 8, and Week 12 (endpoint). Healthy controls provide only cross-sectional baseline data.
- Participant Eligibility and Screening Inclusion criteria for patients: (1) MDD diagnosis confirmed by two senior psychiatrists; (2) HAMD-17 total score ≥17 at baseline; (3) aged 14-60 years; (4) at least junior high school education. Exclusion criteria include: other psychiatric disorders, organic CNS diseases, severe physical illnesses, substance abuse history, physical therapy within the past year, pregnancy/lactation, or significant abnormalities in ECG, routine blood tests, liver/kidney/thyroid function. Written informed consent is obtained from all patients (and legal guardians for minors or cognitively impaired individuals).
- Interventions and Procedures (1) PGx-guided group: Buccal swab samples are collected at baseline for targeted genotyping (chip or sequencing) of key polymorphisms in drug-metabolizing enzymes, transporters, and targets, including CYP2D6, CYP2C19, CYP3A4/5, CYP1A2, CYP2B6, CYP2C9, HTR2A, and SLC6A4. The report classifies patients into ultrarapid, normal, intermediate, or poor metabolizer phenotypes and provides prescribing recommendations for SSRIs (escitalopram, sertraline, fluoxetine, paroxetine, fluvoxamine, citalopram), SNRIs (venlafaxine, duloxetine, milnacipran), NaSSAs (mirtazapine), and others (bupropion). Clinicians prioritize drugs predicted to offer better efficacy and lower risk, adjusting starting doses based on metabolic type.
(2) Conventional group: Buccal swabs are collected but not analyzed (sham procedure to maintain blinding balance). Clinicians prescribe antidepressants following Chinese depression treatment guidelines, based on symptom profiles, prior medication history, and clinical judgment. Both groups allow dose adjustments during follow-up, with all changes documented.
4. Data Acquisition and Multi-Dimensional Biomarker Assessment All participants (including healthy controls) undergo baseline assessments: (1) Demographics and clinical history; (2) Peripheral blood for inflammatory markers (CRP, IL-6), endocrine function (thyroid panel: TSH, FT3, FT4), neurotrophic factor (BDNF), and routine biochemistry (liver/kidney function, glucose, lipids); (3) Urine and stool samples for future metabolomic and gut microbiome analyses; (4) Resting-state fMRI scanning, with primary extraction of voxel-mirrored homotopic connectivity (VMHC), and optional exploration of ALFF and FCD; (5) Scale assessments: HAMD-17, HAMA, and TESS. Follow-up visits (Weeks 4, 8, 12) for patient groups include only scale assessments and adverse event recording, without repeated blood draws or imaging.
5. Outcome Definitions Primary outcome: 12-week response rate, defined as the proportion of patients with ≥50% reduction in HAMD-17 total score from baseline (χ² test between groups).
Secondary outcomes: (1) 12-week remission rate (HAMD-17 ≤7); (2) Trajectory of depressive symptoms across time points (repeated-measures ANOVA); (3) Incidence of treatment-emergent adverse events (TESS); (4) Dropout rate due to adverse events; (5) Concordance between initial drug choice and PGx recommendations (descriptive, intervention group only); (6) Time to reach stable effective dose (survival analysis); (7) Frequency of medication adjustments (Mann-Whitney U test).
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
- Single (Participant)
入排标准
- 年龄范围
- 14 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Clinical diagnosis of Major Depressive Disorder (MDD) according to DSM-5 criteria
- •Age between 18 and 60 years
- •Baseline HAMD-17 total score ≥ 17
- •Ability to provide written informed consent
排除标准
- •History of other psychiatric disorders (e.g., bipolar disorder, schizophrenia)
- •Presence of severe physical illnesses or major central nervous system diseases
- •History of sedative-hypnotic, alcohol, or substance abuse
- •Pregnancy, lactation, or planning to become pregnant during the study
- •Significant abnormalities in ECG, complete blood count, or liver/kidney/thyroid function tests
结局指标
主要结局
Title: 12-Week Response Rate Defined by HAMD-17 Score Reduction
时间窗: From baseline to Week 12.
Unit: percent. The proportion of participants achieving a clinical response, defined as a reduction in HAMD-17 score of 50% or greater from baseline.
次要结局
- 12-Week Remission Rate Defined by HAMD-17 Total Score(Week 12.)
- Longitudinal Trajectory of Depressive Symptoms Assessed by HAMD-17 Over 12 Weeks(Baseline, Week 4, Week 8, and Week 12.)
- Incidence of Treatment-Emergent Adverse Events Assessed by the TESS Scale(From randomization through Week 12.)
- Proportion of Participants Withdrawing Due to Adverse Drug Reactions(From randomization through Week 12.)
- Time to Reach Stable Effective Antidepressant Dose(From randomization through Week 12.)
- Concordance Between PGx Recommendations and Prescribed Medication(Baseline (time of first prescription).)
- Frequency of Antidepressant Regimen Adjustments Within 12 Weeks(From randomization through Week 12.)
- Incidence of Clinically Significant Laboratory Abnormalities(Baseline to Week 12.)