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

NCT ID: NCT02711215

Last Updated: 2019-09-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2020-01-31

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.

Conditions

Major Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Interventions

PET/MR [11C]DASB

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

Intervention Type: DIAGNOSTIC_TEST

Citalopram

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

Intervention Type: 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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Hybrid imaging, Molecular imaging, SERT binding potential; Seropram; Cipralex; Saline, NaCL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Rupert Lanzenberger

Head of the Neuroimaging Labs

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Psychiatry and Psychotherapy, Medical University of Vienna

Vienna, , Austria

Countries

Austria

References

Zadka L, Eggerstorfer B, Buzalewicz I, Vraka C, Rusak A, Godbersen GM, Opalinska A, Unterholzner J, Ulatowska-Jarza A, Philippe C, Haczkiewicz-Lesniak K, Silberbauer LR, Murgas M, Nics L, Hahn A, Hacker M, Gomulkiewicz A, Rujescu D, Podhorska-Okolow M, Lanzenberger R, Gryglewski G. Phenotyping extracellular vesicles and their serotonin transporter cargo in major depressive disorder. J Affect Disord. 2025 Nov 15;389:119740. doi: 10.1016/j.jad.2025.119740. Epub 2025 Jun 21.

Reference Type: DERIVED

PMID: 40550277 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33667309 (View on PubMed)

Other Identifiers

1.6_20180316

Identifier Type: -

Identifier Source: org_study_id