Effects of TBS on 5-HT1A Receptor Binding

Treatment Resistant Depression Clinical Trial

Official title:

Effects of Theta-burst Transcranial Magnetic Stimulation on Serotonin-1A Receptor Binding in Treatment Resistant Depression

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02810717
• Other study ID #: 1.3
• Status: Recruiting
• Phase: N/A
• Start date: December 2016
• Est. completion date: November 2019

Study information

• Verified date: August 2018
• Source: Medical University of Vienna
• Contact: Rupert Lanzenberger, MD
• Phone: +43 40400 35760
• Email: rupert.lanzenberger[@]meduniwien.ac.at
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: November 2019
• Est. primary completion date: November 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant
• Treatment Resistant Depression

Intervention

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.
• 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

Locations

Country	Name	City	State
Austria	Department of Psychiatry and Psychotherapy, Medical University of Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Rupert Lanzenberger

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Depression score using the Hamilton Depression Rating Scale	Depression will be evaluated using the Hamilton Depression Rating Scale	before and after 3 weeks of TBS treatment
Other	Depression score using the Beck Depression Inventory	Depression will be evaluated using the Beck Depression Inventory	before and after 3 weeks of TBS treatment
Other	Global physical activity	assessed using the WHO global physical assessment GPAQ	before and after 3 weeks of TBS treatment
Primary	Regional 5-HT1A receptor binding	5-HT1A receptor binding using the radioligand [carbonyl-11C]WAY100635	before and after 3 weeks of TBS treatment
Secondary	Regional white matter microstructure using DWI-TBSS	The analysis will be performed using tract-based spatial statistics	before and after 3 weeks of TBS treatment
Secondary	Regional white matter microstructure using DWI-Tractography	Tractography will be performed	before and after 3 weeks of TBS treatment
Secondary	Regional grey matter volume using MRI	The analysis will be done using voxel-based morphometry	before and after 3 weeks of TBS treatment
Secondary	Regional brain perfusion	Regional brain perfusion will be evaluated using Arterial Spin Labeling, ASL	before and after 3 weeks of TBS treatment
Secondary	Functional connectivity at rest and during tasks	Functional connectivity will be evaluated using resting state and task fMRI	before and after 3 weeks of TBS treatment

External Links

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