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Effects of TBS on 5-HT1A Receptor Binding

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ClinicalTrials.gov Identifier: NCT02810717
Recruitment Status : Recruiting
First Posted : June 23, 2016
Last Update Posted : August 16, 2018
Sponsor:
Information provided by (Responsible Party):
Rupert Lanzenberger, Medical University of Vienna

Brief Summary:

Background:

Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS) holds promise as an effective treatment for treatment resistant depression (TRD). rTMS has been linked to neuroplastic changes as shown using magnetic resonance imaging (MRI) and positron emission tomography (PET). Alterations in serotonin-1A receptor expression (5-HT1A) have been linked to major depression. Moreover, changes in 5-HT1A receptor binding - observed after pharmacological treatment, as well as after electroconvulsive therapy - has been linked to neuronal adaptations in response to these antidepressant treatments.

Objectives of the study:

Here, the aim is to investigate the effects of TBS over left and right dorsolateral prefrontal cortex on the 5-HT1A receptor binding in patients with TRD using PET. In addition, effects of iTBS on brain structure and function will be determined using functional, structural and perfusion MRI.

Study population:

80 patients with TRD who maintain their original medication regimen will be recruited.

Study design:

Longitudinal, randomized and double-blind clinical trial. 40 patients will receive active TBS, 40 patients will receive sham TBS for treatment duration of three weeks. Before and after three weeks of treatment, patients will be scanned using MRI and PET with the highly specific and selective radiotracer [carbonyl-11C]WAY100635. A follow-up visit and final examination will be performed 2 and 4 weeks after treatment for the active TBS group, respectively. Patients in the sham TBS arm will receive active TBS treatment immediately after the second MRI and PET scan.

Relevance and implications of the study:

This will be the worldwide first multimodal imaging study to investigate the effects of TBS on serotonin-1A receptor binding in TRD using PET. Thus, the study will add crucial knowledge to the existing literature on the effects of TMS on brain structure and function, related to antidepressant efficacy. Moreover, by combining molecular imaging of serotonergic neurotransmission with structural and functional MRI, the proposed study will increase the investigators knowledge on the serotonergic role in shaping brain morphology, microstructure and structural/functional connectivity. Taken together, the study has the potential to contribute to the development of personalized treatment, the reduction of personal suffering and the reduction of costs and occupational disability.


Condition or disease Intervention/treatment Phase
Treatment Resistant Depression Device: theta-burst stimulation using a MagPro X1000 Device: sham stimulation using a MagPro X1000 Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: Effects of Theta-burst Transcranial Magnetic Stimulation on Serotonin-1A Receptor Binding in Treatment Resistant Depression
Study Start Date : December 2016
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : November 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: active TBS
40 patients with TRD will receive active theta-burst stimulation using a MagPro X1000 between the two PET measurements
Device: theta-burst stimulation using a MagPro X1000
TBS over left and right dorsolateral prefrontal cortex for a period of three weeks. iTBS over left DLPFC: 3-pulse 50 Hz bursts will be given every 200ms (at 5 Hz) in 2-second trains with an inter-train interval of 8 seconds. Trains will be repeated 20 to reach a total number of 600 pulses per session. cTBS over right DLPFC: cTBS will comprise uninterrupted bursts to reach a total number of 600 pulses per session. Two sessions per day, separated by 60 minutes; 30 Sessions in total over 3 weeks.
Other Name: repetitive transcranial magnetic stimulation

Sham Comparator: sham TBS
40 patients with TRD will receive sham stimulation using a MagPro X1000 between the two PET measurements. After the second PET scan they will receive active TBS
Device: sham stimulation using a MagPro X1000
Sham TBS with the coil set at 45° against the skull will be performed over left and right dorsolateral prefrontal cortex for a period of three weeks
Other Name: sham transcranial magnetic stimulation




Primary Outcome Measures :
  1. Regional 5-HT1A receptor binding [ Time Frame: before and after 3 weeks of TBS treatment ]
    5-HT1A receptor binding using the radioligand [carbonyl-11C]WAY100635


Secondary Outcome Measures :
  1. Regional white matter microstructure using DWI-TBSS [ Time Frame: before and after 3 weeks of TBS treatment ]
    The analysis will be performed using tract-based spatial statistics

  2. Regional white matter microstructure using DWI-Tractography [ Time Frame: before and after 3 weeks of TBS treatment ]
    Tractography will be performed

  3. Regional grey matter volume using MRI [ Time Frame: before and after 3 weeks of TBS treatment ]
    The analysis will be done using voxel-based morphometry

  4. Regional brain perfusion [ Time Frame: before and after 3 weeks of TBS treatment ]
    Regional brain perfusion will be evaluated using Arterial Spin Labeling, ASL

  5. Functional connectivity at rest and during tasks [ Time Frame: before and after 3 weeks of TBS treatment ]
    Functional connectivity will be evaluated using resting state and task fMRI


Other Outcome Measures:
  1. Depression score using the Hamilton Depression Rating Scale [ Time Frame: before and after 3 weeks of TBS treatment ]
    Depression will be evaluated using the Hamilton Depression Rating Scale

  2. Depression score using the Beck Depression Inventory [ Time Frame: before and after 3 weeks of TBS treatment ]
    Depression will be evaluated using the Beck Depression Inventory

  3. Global physical activity [ Time Frame: before and after 3 weeks of TBS treatment ]
    assessed using the WHO global physical assessment GPAQ



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • DSM-5 diagnosis of single or recurrent major depression
  • HAMD-17 total score of ≥ 18 and a Clinical Global Impression Scale (CGI-S) of ≥ 4
  • Failure of at least two adequate antidepressant treatments
  • Age 18-65 years
  • Right-handedness (assessed with the Edinburgh Handedness Inventory)

Exclusion Criteria:

  • Seizures in medical history
  • Lifetime medical history of major systemic illness, neurological disorders and previous brain injuries
  • Ferromagnetic implants, cardiac pacemaker, deep brain stimulation and other common MRI exclusion criteria
  • Lifetime history of psychotic disorders or current psychotic symptoms
  • Substance abuse or dependence within the last 3 months
  • Borderline personality disorder (based on DSM-5 criteria)
  • Pregnancy
  • Active suicidal intent
  • Benzodiazepines other than Lorazepam > 2mg/d or any dose of an anticonvulsant
  • for participants who participated in an earlier neuroimaging study using ionizing radiation, the total radiation exposure dose of 20 mSv over the last 10 years must not be exceeded, as specified in the legislation on radiation protection.
  • failure to comply with the study protocol or to follow the instructions of the investigating team

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02810717


Contacts
Contact: Rupert Lanzenberger, MD +43 40400 35760 rupert.lanzenberger@meduniwien.ac.at
Contact: Georg Kranz, PhD +43 40400 38250 georg.kranz@meduniwien.ac.at

Locations
Austria
Department of Psychiatry and Psychotherapy, Medical University of Vienna Recruiting
Vienna, Austria, A-1090
Contact: Siegfried Kasper, MD, Prof.    +43-1-40400-3568    sci-biolpsy@meduniwien.ac.at   
Sponsors and Collaborators
Rupert Lanzenberger
Investigators
Principal Investigator: Siegfried Kasper, MD Department of Psychiatry and Psychotherapy, Medical University of Vienna

Additional Information:
Responsible Party: Rupert Lanzenberger, Assoc.-Prof. PD MD, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT02810717     History of Changes
Other Study ID Numbers: 1.3
First Posted: June 23, 2016    Key Record Dates
Last Update Posted: August 16, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: A database that also includes data from this study will be created

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mood Disorders
Mental Disorders