Validation of the predictive value of BDNF -87 methylation for antidepressant treatment success in severely depressed patients—a randomized rater-blinded trial

authored by

Hannah Benedictine Maier, Alexandra Neyazi, Gabriel L. Bundies, Fiona Meyer-Bockenkamp, Stefan Bleich, Hansi Pathak, Yvonne Ziert, Barbara Neuhaus, Franz Josef Müller, Iris Pollmann, Thomas Illig, Stefanie Mücke, Meike Müller, Brinja Kira Möller, Steffen Oeltze-Jafra, Tim Kacprowski, Jan Voges, Fabian Müntefering, Josef Scheiber, Andreas Reif, Mareike Aichholzer, Christine Reif-Leonhard, Maren Schmidt-Kassow, Ulrich Hegerl, Hanna Reich, Stefan Unterecker, Heike Weber, Jürgen Deckert, Nicole Bössel-Debbert, Hans J. Grabe, Michael Lucht, Helge Frieling

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.

Organisation(s)

Institute of Information Processing

External Organisation(s)

Hannover Medical School (MHH)
Otto-von-Guericke University Magdeburg
Kiel University
Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM)
Technische Universität Braunschweig
BioVariance GmbH
Goethe University Frankfurt
Deutsche Gesellschaft für Suizidprävention (DGS)
Julius Maximilian University of Würzburg
University of Greifswald
Max-Planck Institute for Molecular Genetics (MPIMG)
Fraunhofer-Institut für Translationale Medizin und Pharmakologie ITMP

Type

Article

Journal

TRIALS

Volume

25

ISSN

1468-6708

Publication date

09.04.2024

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Medicine (miscellaneous), Pharmacology (medical)

Electronic version(s)

https://doi.org/10.1186/s13063-024-08061-5 (Access: Open)