Clinical trial NCT02810717: Effects of TBS on 5-HT1A Receptor Binding
Official title: Effects of Theta-burst Transcranial Magnetic Stimulation on Serotonin-1A Receptor Binding in Treatment Resistant Depression
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Treatment Resistant Depression
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2016-06-23
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Regional 5-HT1A receptor binding
timeFrame: before and after 3 weeks of TBS treatment
Secondary outcomes:
measure: Regional white matter microstructure using DWI-TBSS
timeFrame: before and after 3 weeks of TBS treatment
measure: Regional white matter microstructure using DWI-Tractography
timeFrame: before and after 3 weeks of TBS treatment
measure: Regional grey matter volume using MRI
timeFrame: before and after 3 weeks of TBS treatment
measure: Regional brain perfusion
timeFrame: before and after 3 weeks of TBS treatment
measure: Functional connectivity at rest and during tasks
timeFrame: before and after 3 weeks of TBS treatment
Other outcomes:
measure: Depression score using the Hamilton Depression Rating Scale
timeFrame: before and after 3 weeks of TBS treatment
measure: Depression score using the Beck Depression Inventory
timeFrame: before and after 3 weeks of TBS treatment
measure: Global physical activity
timeFrame: before and after 3 weeks of TBS treatment
Locations:
city: Vienna
country: Austria
facility: Department of Psychiatry and Psychotherapy, Medical University of Vienna
Study officials:
affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna
name: Siegfried Kasper, MD
role: PRINCIPAL_INVESTIGATOR
References: