Brain-derived neurotrophic factor (BDNF) is essential for antidepressant treatment of major depressive disorder (MDD). Our repeated studies suggest that DNA methylation of a specific CpG site in the promoter region of exon IV of the BDNF gene (CpG -87) might be predictive of the efficacy of monoaminergic antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and others. This trial aims to evaluate whether knowing the biomarker is non-inferior to treatment-as-usual (TAU) regarding remission rates while exhibiting significantly fewer adverse events (AE). The BDNF trial is a prospective, randomized, rater-blinded diagnostic study conducted at five university hospitals in Germany. The study’s main hypothesis is that {1} knowing the methylation status of CpG -87 is non-inferior to not knowing it with respect to the remission rate while it significantly reduces the AE rate in patients experiencing at least one AE. The baseline assessment will occur upon hospitalization and a follow-up assessment on day 49 (± 3). A telephone follow-up will be conducted on day 70 (± 3). A total of 256 patients will be recruited, and methylation will be evaluated in all participants. They will be randomly assigned to either the marker or the TAU group. In the marker group, the methylation results will be shared with both the patient and their treating physician. In the TAU group, neither the patients nor their treating physicians will receive the marker status. The primary endpoints include the rate of patients achieving remission on day 49 (± 3), defined as a score of ≤ 10 on the Hamilton Depression Rating Scale (HDRS-24), and the occurrence of AE. The trial protocol has received approval from the Institutional Review Boards at the five participating universities. This trial holds significance in generating valuable data on a predictive biomarker for antidepressant treatment in patients with MDD. The findings will be shared with study participants, disseminated through professional society meetings, and published in peer-reviewed journals. German Clinical Trial Register DRKS00032503. Registered on 17 August 2023.

中文翻译：

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验证 BDNF -87 甲基化对严重抑郁症患者抗抑郁治疗成功的预测价值——一项随机盲法试验

脑源性神经营养因子（BDNF）对于重度抑郁症（MDD）的抗抑郁治疗至关重要。我们的反复研究表明，BDNF 基因外显子 IV 启动子区 (CpG -87) 特定 CpG 位点的 DNA 甲基化可能可以预测单胺能抗抑郁药的疗效，例如选择性血清素再摄取抑制剂 (SSRI)、血清素-去甲肾上腺素再摄取抑制剂（SNRI）等。该试验旨在评估了解生物标志物在缓解率方面是否不劣于常规治疗 (TAU)，同时不良事件 (AE) 显着减少。 BDNF 试验是一项前瞻性、随机、评估者盲法诊断研究，在德国五家大学医院进行。该研究的主要假设是{1}就缓解率而言，了解 CpG -87 的甲基化状态并不劣于不了解它，同时它会显着降低经历至少一种 AE 的患者的 AE 发生率。基线评估将在住院时进行，后续评估将在第 49 天 (± 3) 天进行。将在第 70 天 (± 3) 天进行电话随访。总共将招募 256 名患者，并对所有参与者的甲基化进行评估。他们将被随机分配到标记组或 TAU 组。在标记物组中，甲基化结果将与患者及其治疗医生共享。在 TAU 组中，患者及其治疗医生都不会收到标记物状态。主要终点包括第 49 天 (± 3) 天缓解的患者率（定义为汉密尔顿抑郁量表 (HDRS-24) 得分 ≤ 10）以及 AE 的发生率。该试验方案已获得五所参与大学的机构审查委员会的批准。该试验对于生成有关重度抑郁症患者抗抑郁治疗的预测生物标志物的有价值的数据具有重要意义。研究结果将与研究参与者分享，通过专业协会会议传播，并在同行评审期刊上发表。德国临床试验注册号 DRKS00032503。注册日期：2023 年 8 月 17 日。