Patient Stratification and Treatment Response Prediction in Neuropharmacotherapy Using Hybrid Positron Emmission Tomography/Magnetic Resconance Imaging (PET/MR)
|ClinicalTrials.gov Identifier: NCT02711215|
Recruitment Status : Active, not recruiting
First Posted : March 17, 2016
Last Update Posted : September 3, 2019
Selective serotonin reuptake inhibitors (SSRIs) raise serotonin (5-HT) in the synaptic cleft and are the current first line of pharmacological antidepressive treatment. Yet, there is a missing link between this first molecular step in their mechanism of action and observed clinical improvement. We have determined to establish a framework combining genuine molecular and functional imaging, i.e. hybrid pharmaco-PET/MR imaging, of the human serotonergic system in order to predict antidepressant treatment response.
- To predict antidepressant treatment response from data obtained using hybrid PET/MR with acute pharmacological challenge.
- To discriminate healthy from depressed subjects using this paradigm.
- To establish models connecting regional changes in occupancy of serotonin transporters (5-HTT) following citalopram infusion, with changes in brain activation and connectivity of major resting-state hub networks.
Design: Randomized, double-blind, placebo-controlled, cross-over mono-center study.
Materials and methods:
40 major depressed (MDD) and 40 healthy subjects will undergo 2 PET/MR scans on a 3T SIEMENS mMR Biograph scanner: 1. challenge with citalopram 8mg 2. placebo (saline). After structural imaging, functional MRI will be continuously acquired. [11C]DASB will be applied using a bolus + constant infusion paradigm to probe 5-HTT binding potentials and monitor 5-HTT occupancy with drug challenge, applied after 70min, in a single session. Scanning will be terminated 80min after challenge. MDD patients will receive subsequent escitalopram treatment with repeated evaluation of response for 3 months.
|Condition or disease||Intervention/treatment||Phase|
|Major Depressive Disorder||Diagnostic Test: PET/MR [11C]DASB Drug: Citalopram Drug: Escitalopram (Mirtazapine/Duloxetine/Venlafaxine) Drug: Placebo||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Investigator)|
|Primary Purpose:||Basic Science|
|Study Start Date :||May 2015|
|Estimated Primary Completion Date :||January 2020|
|Estimated Study Completion Date :||January 2020|
- Diagnostic Test: PET/MR [11C]DASB
2 PET/MR scans will be performed (placebo/citalopram - double-blind randomized cross-over)Other Name: Hybrid imaging, Molecular imaging, SERT binding potential
- Drug: Citalopram
8mg citalopram or placebo (saline) will be applied during PET/MR measurements in a double-blind randomized cross-over designOther Name: Seropram
- Drug: Escitalopram (Mirtazapine/Duloxetine/Venlafaxine)
After completion of imaging procedures, patients will receive treatment with escitalopram 10-20mg. In case of non-response, after 6 weeks, treatment will be switched to either Mirtazapine, Duloxetine or VenlafaxineOther Name: Cipralex
- Drug: Placebo
8mg citalopram or placebo (saline) will be applied during PET/MR measurements in a double-blind randomized cross-over designOther Name: Saline, NaCL
- Hamilton Depression Scale (HDRS) [ Time Frame: 12 weeks ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02711215
|Department of Psychiatry and Psychotherapy, Medical University of Vienna|
|Vienna, Austria, 1090|