Treatment Resistant DepressionNCT02810717
Effects of TBS on 5-HT1A Receptor Binding
A study testing theta-burst stimulation using a MagPro X1000 in people with Treatment Resistant Depression, run by Rupert Lanzenberger at 1 site in Austria.
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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- theta-burst stimulation using a MagPro X1000
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteAustria
- Study dates
- Dec 2016to Nov 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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)
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Austria1 site, 1 recruiting
- Recruiting
Department of Psychiatry and Psychotherapy, Medical University of Vienna
Vienna, A-1090
Siegfried Kasper, MD, Prof., +43-1-40400-3568, sci-biolpsy@meduniwien.ac.at
About this study
Official title: Effects of Theta-burst Transcranial Magnetic Stimulation on Serotonin-1A Receptor Binding in Treatment Resistant Depression
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.
Read more
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
- Being tested
- theta-burst stimulation using a MagPro X1000, sham stimulation using a MagPro X1000
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
theta-burst stimulation using a MagPro X1000Device
Also called repetitive transcranial magnetic stimulation
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 X1000Device
Also called sham transcranial magnetic stimulation
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
| Study group | Role | What they receive |
|---|---|---|
| active TBS | Experimental | 40 patients with TRD will receive active theta-burst stimulation using a MagPro X1000 between the two PET measurements Receives: 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 Receives: Device: sham stimulation using a MagPro X1000 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Regional 5-HT1A receptor binding
5-HT1A receptor binding using the radioligand [carbonyl-11C]WAY100635
Measured: before and after 3 weeks of TBS treatment
Secondary outcomes (5)
Regional white matter microstructure using DWI-TBSS
The analysis will be performed using tract-based spatial statistics
Measured: before and after 3 weeks of TBS treatment
Regional white matter microstructure using DWI-Tractography
Tractography will be performed
Measured: before and after 3 weeks of TBS treatment
Regional grey matter volume using MRI
The analysis will be done using voxel-based morphometry
Measured: before and after 3 weeks of TBS treatment
Regional brain perfusion
Regional brain perfusion will be evaluated using Arterial Spin Labeling, ASL
Measured: before and after 3 weeks of TBS treatment
Functional connectivity at rest and during tasks
Functional connectivity will be evaluated using resting state and task fMRI
Measured: before and after 3 weeks of TBS treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2016 (estimated)
- Study startDec 2016
- Primary completionNov 2019 (estimated)
- Study completionNov 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rupert Lanzenberger
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Rupert Lanzenberger, Medical University of Vienna
- Investigators
- Siegfried Kasper, MD, Principal investigator, Department of Psychiatry and Psychotherapy, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02810717
- Sponsor's protocol ID
- 1.3
- Status last verified
- Aug 2018
- First submitted
- 1 Jun 2016
- Last updated
- 16 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: A database that also includes data from this study will be created
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Theta-burst Transcranial Magnetic Stimulation on Serotonin-1A Receptor Binding in Treatment Resistant Depression
- ClinicalTrials.gov ID
- NCT02810717
- Acronym / sponsor ID
- 1.3
- Conditions
- Treatment Resistant Depression
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Rupert LanzenbergerUniversity, hospital or other
- Study start
- Dec 2016
- Primary completion
- Nov 2019 (estimated)
- Study completion
- Nov 2019 (estimated)
- First posted
- 23 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| active TBS | Experimental | Device: theta-burst stimulation using a MagPro X100040 patients with TRD will receive active theta-burst stimulation using a MagPro X1000 between the two PET measurements |
| sham TBS | Sham comparator | Device: sham stimulation using a MagPro X100040 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| theta-burst stimulation using a MagPro X1000Also: repetitive transcranial magnetic stimulationTBS 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. | Device | active TBS |
| sham stimulation using a MagPro X1000Also: sham transcranial magnetic stimulationSham 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 | Device | sham TBS |
Primary outcome
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
5 secondary outcomes
Regional white matter microstructure using DWI-TBSS
Time frame: before and after 3 weeks of TBS treatment
Regional white matter microstructure using DWI-Tractography
Time frame: before and after 3 weeks of TBS treatment
Regional grey matter volume using MRI
Time frame: before and after 3 weeks of TBS treatment
Regional brain perfusion
Time frame: before and after 3 weeks of TBS treatment
Functional connectivity at rest and during tasks
Time frame: before and after 3 weeks of TBS treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2018.
- NEUROIMAGING LABsLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. A database that also includes data from this study will be created
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Siegfried Kasper, MD principal investigator
Department of Psychiatry and Psychotherapy, Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing theta-burst stimulation using a MagPro X1000 in people with Treatment Resistant Depression, run by Rupert Lanzenberger at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rupert Lanzenberger, MD (+43 40400 35760, rupert.lanzenberger@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Regional 5-HT1A receptor binding (time frame: before and after 3 weeks of TBS treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2018.