DepressionBOSSFRONTNCT02920840
Brain-oscillation Synchronised Stimulation of the Prefrontal Cortex
A study testing Intermittent theta-burst stimulation, Negative-peak-triggered-TMS and Open-loop replay TMS in people with Depression, run by University Hospital Tuebingen at 1 site in Germany.
Trial summary
Combining TMS and EEG, this study investigates a personalized therapeutic non-invasive brain stimulation protocol in patients with major depression, whereby the timing of the TMS pulses is synchronized with the instantaneous phase of ongoing brain oscillations in order to modulate the inter-hemispheric left and right… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Depression
- What is being tested?
- Intermittent theta-burst stimulation, Negative-peak-triggered-TMS and Open-loop replay TMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteGermany
- Study dates
- Sep 2016to Apr 2017
- 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
Subject inclusion criteria
- Subjects are between 18 to 65 years old
- Subjects meet the Diagnostic and Statistical Manual of Mental Disorders (DSM)-4 criteria for current major depressive disorder (MDD), confirmed with the Structured Clinical Interview for DSM-4.
- On the 21-item Hamilton Rating Scale for Depression (HRSD) subjects need to score 8 points or more.
- Subject is in good physical and mental health. Subject understands the study procedures and agrees to participate in the study by giving written informed consent.
- Subject is willing to comply with the study restrictions.
Subject exclusion criteria
- Subject is under the age of legal consent.
- Subject suffers of bipolar disorder.
- Previous failure of nine or more electroconvulsive therapy treatments.
- A current major depressive episode longer than 5 years.
- A history of substance abuse or dependence within the past 2 years.
- Subject suffers of antisocial or borderline personality disorder, active suicidal ideation with plan and/or intent.
- Subject suffers of current symptoms of psychosis.
- Subject has a history of seizure disorder.
- Subject has a history of severe head injury with loss of consciousness.
- Subject had a prior brain surgery, or any other major psychiatric or medical comorbidity.
- Subjects with intake of pro-convulsive medication, e.g. imipramine, amitriptyline, doxepin, nortriptyline, maprotiline, chlorpromazine, clozapine, foscarnet, ganciclovir, ritonavir, amphetamines, cocaine, ecstasy, phencyclidine (PCP, angel's dust), ketamine, gamma-hydroxybutyrate (GHB), alcohol, theophylline, in accord with present consensus guidelines on safety, ethical considerations, and application of TMS in clinical practice and research (Rossi et al. 2009).
- Subjects are allowed to continue their antidepressant medication, but must be on that medication for at least 2 months and on a stable dose for at least 4 weeks (6 weeks in the case of fluoxetine). Drug doses have to be kept constant during the study.
- Patients with need of regular anxiolytic (e.g. benzodiazepine) treatment above 1 mg lorazepam/d.
- Subjects are allowed to continue psychotherapy, but must be treated a minimum of 12 weeks prior to inclusion in the study, and type and frequency of psychotherapy must not be changed during the study period.
- Subject has a cardiac pacemaker, implanted medication pump, intracardiac line, or acute, unstable cardiac disease.
- Subject has an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head (excluding the mouth) that cannot be safely removed.
- Subject has participated in another study within 2 weeks prior to the first study visit.
- Subject has contra-indications to MRI scans or does not agree that (1) the scans are obtained for research purposes only and will not be evaluated by a qualified neuroradiologist; if an abnormality is present, this may well not be noticed by the doctors, scientists and other staff involved in the study and handling the MRI data; and that (2) if any of the staff involved in the study do suspect a relevant abnormality to be present in any of the scans, they will reveal this to the subject so that a further diagnostic workup can be conducted outside of the study.
- Subject is pregnant or trying to get pregnant.
- Women of childbearing age should avoid.
- Contraindications to an MRI
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Neurology Hospital
Tübingen, Baden-Wurttemberg, 72076
About this study
Official title: Brain-oscillation Synchronised Stimulation of the Prefrontal Cortex: Development and Validation of a Personalized Closed-loop TMS Protocol for the Treatment of Major Depression
Combining TMS and EEG, this study investigates a personalized therapeutic non-invasive brain stimulation protocol in patients with major depression, whereby the timing of the TMS pulses is synchronized with the instantaneous phase of ongoing brain oscillations in order to modulate the inter-hemispheric left and right dorso-lateral prefrontal cortical brain network.
Read the detailed description
Major depressive disorder is a severe psychiatric illness with a lifetime prevalence of about 8-16%. Many patients fail to achieve complete remission of symptoms under antidepressant medication, with about 10% of patients being chronically resistant to several psychopharmacological treatments. Development of alternative non-pharmacological treatments is therefore essential to improve patient care.
Repetitive transcranial magnetic stimulation (rTMS) offers therapeutic potential in this context. Current protocols apply high-frequency rTMS over left dorsolateral prefrontal cortex (DLPFC) to reverse the increased alpha-band oscillatory activity and cortical hypo-excitability in patients with depression. However, translation of rTMS therapy into routine clinical practice has been limited due to low efficacy and high inter-individual variability.
This study aims to optimize rTMS stimulation protocols for MDD by deterministically coupling the timing of TMS to the ongoing oscillatory neural activity in the underlying cortex as measured in real-time with high-density surface EEG. It is hypothesized that alpha phase-locked rTMS of the left DLPFC reverses increased alpha-band oscillatory activity and cortical hypo-excitability more efficiently than current open-loop rTMS protocols used in the treatment of MDD.
- Conditions
- Depression
- Being tested
- Intermittent theta-burst stimulation, Negative-peak-triggered-TMS, Open-loop replay TMS
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intermittent theta-burst stimulationDevice
see associated arm/group description
Negative-peak-triggered-TMSDevice
see associated arm/group description
Open-loop replay TMSDevice
see associated arm/group description
| Study group | Role | What they receive |
|---|---|---|
| Intermittent theta-burst stimulation | Active comparator | Intervention: application of 200 TMS triplet bursts (at 100 Hz, inter-burst interval 200ms) over left dorsolateral prefrontal cortex Receives: Device: Intermittent theta-burst stimulation |
| Negative-peak-triggered-TMS | Experimental | Intervention: application of 200 brain-state dependent 100 Hz TMS triplet bursts triggered at the negative peak phase of the ongoing endogenous alpha-band oscillation (as detected by surface EEG over left dlPFC) Receives: Device: Negative-peak-triggered-TMS |
| Open-loop replay TMS | Active comparator | Intervention: application of the same sequence of TMS pulses as in condition "Negative-peak-triggered-TMS", i.e. irrespective of ongoing brain state over left dlPFC Receives: Device: Open-loop replay TMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in cortical excitability 30 minutes after the intervention
TMS-evoked EEG potentials from left dlPFC
Measured: 30 minutes
Secondary outcomes (2)
Change from baseline in EEG alpha power 30 minutes after the intervention
Left vs. right dlPFC relative spectral power in 8-12 Hz frequency band
Measured: 30 minutes
Change from baseline in verbal working memory performance 30 minutes after the intervention
Verbal working memory task
Measured: 30 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2016 (estimated)
- Study startSep 2016
- Primary completionApr 2017
- Study completionApr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by University Hospital TuebingenThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Brigitte Zrenner, MD, Study director, University Neurology Hospital TübingenFlorian Müller-Dahlhaus, MD, Study director, University Neurology Hospital TübingenUlf Ziemann, MD, Principal investigator, University Neurology Hospital TübingenAndreas J Fallgatter, MD, Principal investigator, University Psychiatry Hospital TübingenSurjo Soekadar, MD, Study director, University Psychiatry Hospital Tübingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02920840
- Sponsor's protocol ID
- BNP2016-03
- Acronym
- BOSSFRONT
- Status last verified
- Sep 2016
- First submitted
- 26 Sep 2016
- Last updated
- 9 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain-oscillation Synchronised Stimulation of the Prefrontal Cortex: Development and Validation of a Personalized Closed-loop TMS Protocol for the Treatment of Major Depression
- ClinicalTrials.gov ID
- NCT02920840
- Acronym / sponsor ID
- BOSSFRONT / BNP2016-03
- Conditions
- Depression
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Study start
- Sep 2016
- Primary completion
- Apr 2017 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 30 Sep 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.
Combining TMS and EEG, this study investigates a personalized therapeutic non-invasive brain stimulation protocol in patients with major depression, whereby the timing of the TMS pulses is synchronized with the instantaneous phase of ongoing brain oscillations in order to modulate the inter-hemispheric left and right dorso-lateral prefrontal cortical brain network.
Detailed description
Major depressive disorder is a severe psychiatric illness with a lifetime prevalence of about 8-16%. Many patients fail to achieve complete remission of symptoms under antidepressant medication, with about 10% of patients being chronically resistant to several psychopharmacological treatments. Development of alternative non-pharmacological treatments is therefore essential to improve patient care.
Repetitive transcranial magnetic stimulation (rTMS) offers therapeutic potential in this context. Current protocols apply high-frequency rTMS over left dorsolateral prefrontal cortex (DLPFC) to reverse the increased alpha-band oscillatory activity and cortical hypo-excitability in patients with depression. However, translation of rTMS therapy into routine clinical practice has been limited due to low efficacy and high inter-individual variability.
This study aims to optimize rTMS stimulation protocols for MDD by deterministically coupling the timing of TMS to the ongoing oscillatory neural activity in the underlying cortex as measured in real-time with high-density surface EEG. It is hypothesized that alpha phase-locked rTMS of the left DLPFC reverses increased alpha-band oscillatory activity and cortical hypo-excitability more efficiently than current open-loop rTMS protocols used in the treatment of MDD.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Intermittent theta-burst stimulation | Active comparator | Device: Intermittent theta-burst stimulationIntervention: application of 200 TMS triplet bursts (at 100 Hz, inter-burst interval 200ms) over left dorsolateral prefrontal cortex |
| Negative-peak-triggered-TMS | Experimental | Device: Negative-peak-triggered-TMSIntervention: application of 200 brain-state dependent 100 Hz TMS triplet bursts triggered at the negative peak phase of the ongoing endogenous alpha-band oscillation (as detected by surface EEG over left dlPFC) |
| Open-loop replay TMS | Active comparator | Device: Open-loop replay TMSIntervention: application of the same sequence of TMS pulses as in condition "Negative-peak-triggered-TMS", i.e. irrespective of ongoing brain state over left dlPFC |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| Intermittent theta-burst stimulationsee associated arm/group description | Device | Intermittent theta-burst stimulation |
| Negative-peak-triggered-TMSsee associated arm/group description | Device | Negative-peak-triggered-TMS |
| Open-loop replay TMSsee associated arm/group description | Device | Open-loop replay TMS |
Primary outcome
Change from baseline in cortical excitability 30 minutes after the intervention
Time frame: 30 minutes
TMS-evoked EEG potentials from left dlPFC
2 secondary outcomes
Change from baseline in EEG alpha power 30 minutes after the intervention
Time frame: 30 minutes
Change from baseline in verbal working memory performance 30 minutes after the intervention
Time frame: 30 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2020.
- Individual participant dataSharing planned: Undecided
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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.
Brigitte Zrenner, MD study director
University Neurology Hospital Tübingen
Florian Müller-Dahlhaus, MD study director
University Neurology Hospital Tübingen
Ulf Ziemann, MD principal investigator
University Neurology Hospital Tübingen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intermittent theta-burst stimulation, Negative-peak-triggered-TMS and Open-loop replay TMS in people with Depression, run by University Hospital Tuebingen at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: finished, as of the sponsor's last update on 9 Sep 2020. 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 Germany. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in cortical excitability 30 minutes after the intervention (time frame: 30 minutes). 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 9 Sep 2020.