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Predicting Treatment Outcome in Major Depressive Disorder Using Serotonin 4 Receptor PET Brain Imaging, Functional MRI, Cognitive-, EEG-Based, and Peripheral Biomarkers: A NeuroPharm Open Label Clinical Trial Protocol

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@article{d922b95124b742bdad42d9b804dd56c8,
title = "Predicting Treatment Outcome in Major Depressive Disorder Using Serotonin 4 Receptor PET Brain Imaging, Functional MRI, Cognitive-, EEG-Based, and Peripheral Biomarkers: A NeuroPharm Open Label Clinical Trial Protocol",
abstract = "Background: Between 30 and 50% of patients with major depressive disorder (MDD) do not respond sufficiently to antidepressant regimens. The conventional pharmacological treatments predominantly target serotonergic brain signaling but better tools to predict treatment response and identify relevant subgroups of MDD are needed to support individualized and mechanistically targeted treatment strategies. The aim of this study is to investigate antidepressant-free patients with MDD using neuroimaging, electrophysiological, molecular, cognitive, and clinical examinations and evaluate their ability to predict clinical response to SSRI treatment as individual or combined predictors.Methods: We will include 100 untreated patients with moderate to severe depression (>17 on the Hamilton Depression Rating Scale 17) in a non-randomized open clinical trial. We will collect data from serotonin 4 receptor positron emission tomography (PET) brain scans, functional magnetic resonance imaging (fMRI), electroencephalogram (EEG), cognitive tests, psychometry, and peripheral biomarkers, before (at baseline), during, and after 12 weeks of standard antidepressant treatment. Patients will be treated with escitalopram, and in case of non-response at week 4 or intolerable side effects, offered to switch to a second line treatment with duloxetine. Our primary outcome (treatment response) is assessed using the Hamilton depression rating subscale 6-item scores at week 8, compared to baseline. In a subset of the patients (n = ~40), we will re-assess the neurobiological response (using PET, fMRI, and EEG) 8 weeks after initiated pharmacological antidepressant treatment, to map neurobiological signatures of treatment responses. Data from matched controls will either be collected or is already available from other cohorts.Discussion: The extensive investigational program with follow-up in this large cohort of participants provides a unique possibility to (a) uncover potential biomarkers for antidepressant treatment response, (b) apply the findings for future stratification of MDD, (c) advance the understanding of pathophysiological underpinnings of MDD, and (d) uncover how putative biomarkers change in response to 8 weeks of pharmacological antidepressant treatment. Our data can pave the way for a precision medicine approach for optimized treatment of MDD and also provides a resource for future research and data sharing.Clinical Trial Registration: The study was registered at clinicaltrials.gov prior to initiation (NCT02869035; 08.16.2016, URL: https://clinicaltrials.gov/ct2/results?cond=&term=NCT02869035&cntry=&state=&city=&dist=).",
keywords = "biomarker, cognition, electroencephalogram, functional magnetic resonance imaging, major depressive disorder, positron emission tomography, serotonin 4 receptor, treatment response",
author = "Kristin K{\"o}hler-Forsberg and Anders Jorgensen and Dam, {Vibeke H} and Stenb{\ae}k, {Dea Siggaard} and Fisher, {Patrick M} and Cheng-Teng Ip and Melanie Ganz and Poulsen, {Henrik Enghusen} and Annamaria Giraldi and Brice Ozenne and J{\o}rgensen, {Martin Balslev} and Knudsen, {Gitte Moos} and Frokjaer, {Vibe Gedsoe}",
note = "Copyright {\textcopyright} 2020 K{\"o}hler-Forsberg, Jorgensen, Dam, Stenb{\ae}k, Fisher, Ip, Ganz, Poulsen, Giraldi, Ozenne, J{\o}rgensen, Knudsen and Frokjaer.",
year = "2020",
doi = "10.3389/fpsyt.2020.00641",
language = "English",
volume = "11",
pages = "641",
journal = "Frontiers in Psychiatry",
issn = "1664-0640",
publisher = "Frontiers Research Foundation",

}

RIS

TY - JOUR

T1 - Predicting Treatment Outcome in Major Depressive Disorder Using Serotonin 4 Receptor PET Brain Imaging, Functional MRI, Cognitive-, EEG-Based, and Peripheral Biomarkers

T2 - A NeuroPharm Open Label Clinical Trial Protocol

AU - Köhler-Forsberg, Kristin

AU - Jorgensen, Anders

AU - Dam, Vibeke H

AU - Stenbæk, Dea Siggaard

AU - Fisher, Patrick M

AU - Ip, Cheng-Teng

AU - Ganz, Melanie

AU - Poulsen, Henrik Enghusen

AU - Giraldi, Annamaria

AU - Ozenne, Brice

AU - Jørgensen, Martin Balslev

AU - Knudsen, Gitte Moos

AU - Frokjaer, Vibe Gedsoe

N1 - Copyright © 2020 Köhler-Forsberg, Jorgensen, Dam, Stenbæk, Fisher, Ip, Ganz, Poulsen, Giraldi, Ozenne, Jørgensen, Knudsen and Frokjaer.

PY - 2020

Y1 - 2020

N2 - Background: Between 30 and 50% of patients with major depressive disorder (MDD) do not respond sufficiently to antidepressant regimens. The conventional pharmacological treatments predominantly target serotonergic brain signaling but better tools to predict treatment response and identify relevant subgroups of MDD are needed to support individualized and mechanistically targeted treatment strategies. The aim of this study is to investigate antidepressant-free patients with MDD using neuroimaging, electrophysiological, molecular, cognitive, and clinical examinations and evaluate their ability to predict clinical response to SSRI treatment as individual or combined predictors.Methods: We will include 100 untreated patients with moderate to severe depression (>17 on the Hamilton Depression Rating Scale 17) in a non-randomized open clinical trial. We will collect data from serotonin 4 receptor positron emission tomography (PET) brain scans, functional magnetic resonance imaging (fMRI), electroencephalogram (EEG), cognitive tests, psychometry, and peripheral biomarkers, before (at baseline), during, and after 12 weeks of standard antidepressant treatment. Patients will be treated with escitalopram, and in case of non-response at week 4 or intolerable side effects, offered to switch to a second line treatment with duloxetine. Our primary outcome (treatment response) is assessed using the Hamilton depression rating subscale 6-item scores at week 8, compared to baseline. In a subset of the patients (n = ~40), we will re-assess the neurobiological response (using PET, fMRI, and EEG) 8 weeks after initiated pharmacological antidepressant treatment, to map neurobiological signatures of treatment responses. Data from matched controls will either be collected or is already available from other cohorts.Discussion: The extensive investigational program with follow-up in this large cohort of participants provides a unique possibility to (a) uncover potential biomarkers for antidepressant treatment response, (b) apply the findings for future stratification of MDD, (c) advance the understanding of pathophysiological underpinnings of MDD, and (d) uncover how putative biomarkers change in response to 8 weeks of pharmacological antidepressant treatment. Our data can pave the way for a precision medicine approach for optimized treatment of MDD and also provides a resource for future research and data sharing.Clinical Trial Registration: The study was registered at clinicaltrials.gov prior to initiation (NCT02869035; 08.16.2016, URL: https://clinicaltrials.gov/ct2/results?cond=&term=NCT02869035&cntry=&state=&city=&dist=).

AB - Background: Between 30 and 50% of patients with major depressive disorder (MDD) do not respond sufficiently to antidepressant regimens. The conventional pharmacological treatments predominantly target serotonergic brain signaling but better tools to predict treatment response and identify relevant subgroups of MDD are needed to support individualized and mechanistically targeted treatment strategies. The aim of this study is to investigate antidepressant-free patients with MDD using neuroimaging, electrophysiological, molecular, cognitive, and clinical examinations and evaluate their ability to predict clinical response to SSRI treatment as individual or combined predictors.Methods: We will include 100 untreated patients with moderate to severe depression (>17 on the Hamilton Depression Rating Scale 17) in a non-randomized open clinical trial. We will collect data from serotonin 4 receptor positron emission tomography (PET) brain scans, functional magnetic resonance imaging (fMRI), electroencephalogram (EEG), cognitive tests, psychometry, and peripheral biomarkers, before (at baseline), during, and after 12 weeks of standard antidepressant treatment. Patients will be treated with escitalopram, and in case of non-response at week 4 or intolerable side effects, offered to switch to a second line treatment with duloxetine. Our primary outcome (treatment response) is assessed using the Hamilton depression rating subscale 6-item scores at week 8, compared to baseline. In a subset of the patients (n = ~40), we will re-assess the neurobiological response (using PET, fMRI, and EEG) 8 weeks after initiated pharmacological antidepressant treatment, to map neurobiological signatures of treatment responses. Data from matched controls will either be collected or is already available from other cohorts.Discussion: The extensive investigational program with follow-up in this large cohort of participants provides a unique possibility to (a) uncover potential biomarkers for antidepressant treatment response, (b) apply the findings for future stratification of MDD, (c) advance the understanding of pathophysiological underpinnings of MDD, and (d) uncover how putative biomarkers change in response to 8 weeks of pharmacological antidepressant treatment. Our data can pave the way for a precision medicine approach for optimized treatment of MDD and also provides a resource for future research and data sharing.Clinical Trial Registration: The study was registered at clinicaltrials.gov prior to initiation (NCT02869035; 08.16.2016, URL: https://clinicaltrials.gov/ct2/results?cond=&term=NCT02869035&cntry=&state=&city=&dist=).

KW - biomarker

KW - cognition

KW - electroencephalogram

KW - functional magnetic resonance imaging

KW - major depressive disorder

KW - positron emission tomography

KW - serotonin 4 receptor

KW - treatment response

UR - http://www.scopus.com/inward/record.url?scp=85089217497&partnerID=8YFLogxK

U2 - 10.3389/fpsyt.2020.00641

DO - 10.3389/fpsyt.2020.00641

M3 - Journal article

C2 - 32792991

VL - 11

SP - 641

JO - Frontiers in Psychiatry

JF - Frontiers in Psychiatry

SN - 1664-0640

M1 - 641

ER -

ID: 60849492