Patient Stratification and Treatment Response Prediction in Neuropharmacotherapy Using Hybrid Positron Emmission Tomography/Magnetic Resconance Imaging (PET/MR)

Summary

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.

Objectives:

1. To predict antidepressant treatment response from data obtained using hybrid PET/MR with acute pharmacological challenge.
2. To discriminate healthy from depressed subjects using this paradigm.
3. 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.

Conditions

• Major Depressive Disorder

Interventions

DIAGNOSTIC_TEST

PET/MR [11C]DASB

2 PET/MR scans will be performed (placebo/citalopram - double-blind randomized cross-over)

DRUG

Citalopram

8mg citalopram or placebo (saline) will be applied during PET/MR measurements in a double-blind randomized cross-over design

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 Venlafaxine

DRUG

Placebo

8mg citalopram or placebo (saline) will be applied during PET/MR measurements in a double-blind randomized cross-over design

Sponsors & Collaborators

• Medical University of Vienna

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2015-05-31

Primary Completion

2020-01-31

Completion

2020-01-31

Countries

• Austria

Study Locations