Effects of TBS on 5-HT1A Receptor Binding

NCT02810717 | Unknown

• 1 other identifier: 1.3
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Regional 5-HT1A receptor binding

  5-HT1A receptor binding using the radioligand \[carbonyl-11C\]WAY100635

  before and after 3 weeks of TBS treatment

Secondary Outcomes (5)

• Regional white matter microstructure using DWI-TBSS

  before and after 3 weeks of TBS treatment

• Regional white matter microstructure using DWI-Tractography

  before and after 3 weeks of TBS treatment

• Regional grey matter volume using MRI

  before and after 3 weeks of TBS treatment

• Regional brain perfusion

  before and after 3 weeks of TBS treatment

• Functional connectivity at rest and during tasks

  before and after 3 weeks of TBS treatment

Other Outcomes (3)

• Depression score using the Hamilton Depression Rating Scale

  before and after 3 weeks of TBS treatment

• Depression score using the Beck Depression Inventory

  before and after 3 weeks of TBS treatment

• Global physical activity

  before and after 3 weeks of TBS treatment

Study Arms (2)

active TBS

EXPERIMENTAL

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

sham TBS

SHAM COMPARATOR

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

Interventions

theta-burst stimulation using a MagPro X1000 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.

Also known as: repetitive transcranial magnetic stimulation

active TBS

sham stimulation using a MagPro X1000 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

Also known as: sham transcranial magnetic stimulation

sham TBS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Rupert Lanzenberger: lead

Study Sites (1)

Department of Psychiatry and Psychotherapy, Medical University of Vienna

Vienna, A-1090, Austria

RECRUITING

Related Links

• NEUROIMAGING LABs

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Siegfried Kasper, MD

  Department of Psychiatry and Psychotherapy, Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rupert Lanzenberger, MD

CONTACT

+43 40400 35760; rupert.lanzenberger@meduniwien.ac.at

Georg Kranz, PhD

CONTACT

+43 40400 38250; georg.kranz@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assoc.-Prof. PD MD

Study Record Dates

• First Submitted: June 1, 2016
• First Posted: June 23, 2016
• Study Start: December 1, 2016
• Primary Completion: November 1, 2019
• Study Completion: November 1, 2019
• Last Updated: August 16, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)