Clinical trial NCT02711215: Patient Stratification and Treatment Response Prediction in Neuropharmacotherapy Using Hybrid Positron Emmission Tomography/Magnetic Resconance Imaging (PET/MR)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Major Depressive Disorder
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2016-03-17
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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:

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.


Eligibility criteria: 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

Primary outcomes:
measure: Hamilton Depression Scale (HDRS)
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Department of Psychiatry and Psychotherapy, Medical University of Vienna
Study officials:
References:
citation: Seiger R, Gryglewski G, Klobl M, Kautzky A, Godbersen GM, Rischka L, Vanicek T, Hienert M, Unterholzner J, Silberbauer LR, Michenthaler P, Handschuh P, Hahn A, Kasper S, Lanzenberger R. The Influence of Acute SSRI Administration on White Matter Microstructure in Patients Suffering From Major Depressive Disorder and Healthy Controls. Int J Neuropsychopharmacol. 2021 Jul 23;24(7):542-550. doi: 10.1093/ijnp/pyab008.