Patient Stratification and Treatment Response Prediction in Neuropharmacotherapy Using Hybrid Positron Emmission Tomography/Magnetic Resconance Imaging (PET/MR)
Primary Purpose
Major Depressive Disorder
Status
Unknown status
Phase
Phase 4
Locations
Austria
Study Type
Interventional
Intervention
PET/MR [11C]DASB
Citalopram
Escitalopram (Mirtazapine/Duloxetine/Venlafaxine)
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Major Depressive Disorder
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
Sites / Locations
- Department of Psychiatry and Psychotherapy, Medical University of Vienna
Outcomes
Primary Outcome Measures
Hamilton Depression Scale (HDRS)
Secondary Outcome Measures
Full Information
NCT ID
NCT02711215
First Posted
March 14, 2016
Last Updated
August 30, 2019
Sponsor
Medical University of Vienna
1. Study Identification
Unique Protocol Identification Number
NCT02711215
Brief Title
Patient Stratification and Treatment Response Prediction in Neuropharmacotherapy Using Hybrid Positron Emmission Tomography/Magnetic Resconance Imaging (PET/MR)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Unknown status
Study Start Date
May 2015 (undefined)
Primary Completion Date
January 2020 (Anticipated)
Study Completion Date
January 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of Vienna
4. Oversight
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Diagnostic Test
Intervention Name(s)
PET/MR [11C]DASB
Other Intervention Name(s)
Hybrid imaging, Molecular imaging, SERT binding potential
Intervention Description
2 PET/MR scans will be performed (placebo/citalopram - double-blind randomized cross-over)
Intervention Type
Drug
Intervention Name(s)
Citalopram
Other Intervention Name(s)
Seropram
Intervention Description
8mg citalopram or placebo (saline) will be applied during PET/MR measurements in a double-blind randomized cross-over design
Intervention Type
Drug
Intervention Name(s)
Escitalopram (Mirtazapine/Duloxetine/Venlafaxine)
Other Intervention Name(s)
Cipralex
Intervention Description
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
Intervention Name(s)
Placebo
Other Intervention Name(s)
Saline, NaCL
Intervention Description
8mg citalopram or placebo (saline) will be applied during PET/MR measurements in a double-blind randomized cross-over design
Primary Outcome Measure Information:
Title
Hamilton Depression Scale (HDRS)
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Facility Information:
Facility Name
Department of Psychiatry and Psychotherapy, Medical University of Vienna
City
Vienna
ZIP/Postal Code
1090
Country
Austria
12. IPD Sharing Statement
Citations:
PubMed Identifier
33667309
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.
Results Reference
derived
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Patient Stratification and Treatment Response Prediction in Neuropharmacotherapy Using Hybrid Positron Emmission Tomography/Magnetic Resconance Imaging (PET/MR)
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