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

Sponsor

Medical University of Vienna (Other)

Overall Status

Unknown status

CT.gov ID

NCT02711215

Collaborator

(none)

Enrollment

Location

Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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:

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 Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Study Start Date :

May 1, 2015

Anticipated Primary Completion Date :

Jan 1, 2020

Anticipated Study Completion Date :

Jan 1, 2020

Outcome Measures

Primary Outcome Measures

Hamilton Depression Scale (HDRS) [12 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

General health based on medical history, physical examination and structured clinical interview for DSM-IV (SCID)
HAM-D≥18 (patients)
Willingness and competence to sign the informed consent form
Age 18 to 55 years

Exclusion Criteria:

Any medical, psychiatric or neurological illness (other than MDD)
Current or former psychopharmacological treatment
Current or former substance abuse
Pregnancy
Any implant or stainless steel graft or any other contraindications for MRI
Failure to comply with the study protocol or to follow the instructions of the investigating team
Participation in studies involving radiation exposure in the past 10 years.
Body mass index <17 or >30