Details
| Original language | English |
|---|---|
| Article number | 247 |
| Journal | TRIALS |
| Volume | 25 |
| Issue number | 1 |
| Publication status | Published - 9 Apr 2024 |
Abstract
Background: 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). Methods: 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. Ethics and dissemination: 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. Trial registration: German Clinical Trial Register DRKS00032503. Registered on 17 August 2023.
Keywords
- BDNF, Biomarker, Major depressive disorder, RCT
ASJC Scopus subject areas
- Medicine(all)
- Medicine (miscellaneous)
- Medicine(all)
- Pharmacology (medical)
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In: TRIALS, Vol. 25, No. 1, 247, 09.04.2024.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Validation of the predictive value of BDNF -87 methylation for antidepressant treatment success in severely depressed patients—a randomized rater-blinded trial
AU - Maier, Hannah Benedictine
AU - Neyazi, Alexandra
AU - Bundies, Gabriel L.
AU - Meyer-Bockenkamp, Fiona
AU - Bleich, Stefan
AU - Pathak, Hansi
AU - Ziert, Yvonne
AU - Neuhaus, Barbara
AU - Müller, Franz Josef
AU - Pollmann, Iris
AU - Illig, Thomas
AU - Mücke, Stefanie
AU - Müller, Meike
AU - Möller, Brinja Kira
AU - Oeltze-Jafra, Steffen
AU - Kacprowski, Tim
AU - Voges, Jan
AU - Müntefering, Fabian
AU - Scheiber, Josef
AU - Reif, Andreas
AU - Aichholzer, Mareike
AU - Reif-Leonhard, Christine
AU - Schmidt-Kassow, Maren
AU - Hegerl, Ulrich
AU - Reich, Hanna
AU - Unterecker, Stefan
AU - Weber, Heike
AU - Deckert, Jürgen
AU - Bössel-Debbert, Nicole
AU - Grabe, Hans J.
AU - Lucht, Michael
AU - Frieling, Helge
N1 - Funding Information: HBM is supported by the PRACTIS-Clinician Scientist Program of Hannover Medical School, funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, ME3696/3-1) \u2013 Project-ID 413617135. Funding Information: HBM took part in educational events sponsored by Livanova and Rovi. AN received lecture fees from Novartis and Merck. HJG has received travel grants and speakers\u2019 honoraria from Fresenius Medical Care, Neuraxpharm, and Janssen Cilag as well as research funding from Fresenius Medical Care. AR has received honoraria for lectures and/or advisory boards from Janssen, Boehringer Ingelheim, COMPASS, SAGE/Biogen, LivaNova, Medice, Shire/Takeda, MSD, and cyclerion. Also, he has received research grants from Medice and Janssen. CRL Advisory boards: Janssen und LivaNova, speaker honoraria: Janssen, LivaNova, diaplan, derCampus. HF received speakers\u2019 honoraria and served as an advisor for Recordati Pharma GmbH and Janssen-Cilag GmbH. Funding Information: Open Access funding enabled and organized by Projekt DEAL. The project is funded by the Federal Ministry of Education and Research (BMBF) (grant number: 01EK2204A). The funds received through this grant will be utilized for the execution of this and the overarching P4D project. The funder has no role in the conception, design, conduct, oversight, analysis, interpretation, write-up, review, or approval of the manuscript or the decision to submit the manuscript for publication.
PY - 2024/4/9
Y1 - 2024/4/9
N2 - Background: 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). Methods: 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. Ethics and dissemination: 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. Trial registration: German Clinical Trial Register DRKS00032503. Registered on 17 August 2023.
AB - Background: 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). Methods: 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. Ethics and dissemination: 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. Trial registration: German Clinical Trial Register DRKS00032503. Registered on 17 August 2023.
KW - BDNF
KW - Biomarker
KW - Major depressive disorder
KW - RCT
UR - http://www.scopus.com/inward/record.url?scp=85190297648&partnerID=8YFLogxK
U2 - 10.1186/s13063-024-08061-5
DO - 10.1186/s13063-024-08061-5
M3 - Article
C2 - 38594753
AN - SCOPUS:85190297648
VL - 25
JO - TRIALS
JF - TRIALS
SN - 1468-6708
IS - 1
M1 - 247
ER -