Effects of TBS on 5-HT1A Receptor Binding

NCT ID: NCT02810717

Last Updated: 2018-08-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2019-11-30

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.

Conditions

Treatment Resistant Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

active TBS

40 patients with TRD will receive active theta-burst stimulation using a MagPro X1000 between the two PET measurements

Group Type: EXPERIMENTAL

theta-burst stimulation using a MagPro X1000

Intervention Type: DEVICE

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 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

Group Type: SHAM_COMPARATOR

sham stimulation using a MagPro X1000

Intervention Type: DEVICE

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

Interventions

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.

Intervention Type: 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

Intervention Type: DEVICE

Other Intervention Names

repetitive transcranial magnetic stimulation; sham transcranial magnetic stimulation

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
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rupert Lanzenberger

OTHER

Sponsor Role: lead

Responsible Party

Rupert Lanzenberger

Assoc.-Prof. PD MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Siegfried Kasper, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Psychiatry and Psychotherapy, Medical University of Vienna

Locations

Department of Psychiatry and Psychotherapy, Medical University of Vienna

Vienna, , Austria

Site Status: RECRUITING

Countries

Austria

Central Contacts

Rupert Lanzenberger, MD

Role: CONTACT

rupert.lanzenberger@meduniwien.ac.at

+43 40400 35760

Georg Kranz, PhD

Role: CONTACT

georg.kranz@meduniwien.ac.at

+43 40400 38250

Facility Contacts

Siegfried Kasper, MD, Prof.

Role: primary

sci-biolpsy@meduniwien.ac.at

+43-1-40400-3568

Related Links

http://www.meduniwien.ac.at/neuroimaging/

NEUROIMAGING LABs

Other Identifiers

1.3

Identifier Type: -

Identifier Source: org_study_id