Major Depressive DisorderNCT04526002
The Utility of Concurrent TBS/fNIRS for Antidepressant Treatment Optimization
A study testing Theta-burst stimulation (TBS) in people with Major Depressive Disorder, run by Dr Georg Kranz at 1 site in Hong Kong.
Trial summary
Repetitive transcranial magnetic stimulation (rTMS) with theta bursts (i.e. TBS) of the dorsolateral prefrontal cortex (DLPFC) is an innovative treatment for major depressive disorder (MDD). Indeed, the U. S. Food and Drug Administration (FDA) has only recently approved TBS (in August 2018). Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Theta-burst stimulation (TBS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Mar 2023to 15 May 2024
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- MDD (DSM-5), HAMD17 ≥18, approval for TBS treatment by the physician in charge, stable antidepressive medication 4 weeks before treatment (the sample will include at least 20 drug-naïve patients in order to avoid confounding effects of medication for testing hypothesis 4).
- age between 18 and 60, right-handedness.
Who cannot join
- a history of brain surgery, head injury, stroke or neurodegenerative disorder, diagnosis of personality disorder, psychotic features, active suicidal intent, severe somatic comorbidities, cardiac pacemakers, deep brain stimulation, intracranial metallic particles, history of seizures, antiepileptics and benzodiazepines corresponding to a dose of >1 mg lorazepam/d, substance dependence or abuse, if it is the primary clinical problem.
- HC group:
- a current or previous diagnosis of a psychiatric, neurological disorder or severe internal illness, common contraindications to rTMS,26 and a psychiatric disorder in their first-degree relatives.
Trial locations and contacts
1 site in 1 country.
About this study
Repetitive transcranial magnetic stimulation (rTMS) with theta bursts (i.e. TBS) of the dorsolateral prefrontal cortex (DLPFC) is an innovative treatment for major depressive disorder (MDD). Indeed, the U. S. Food and Drug Administration (FDA) has only recently approved TBS (in August 2018). However, fewer than 50% of patients show sufficient response to this treatment; markers for response prediction are urgently needed. Moreover, there is a lack of knowledge of the mechanism of action of TBS of the DLPFC. This is due to difficulties of directly measuring prefrontal stimulation effects, as compared to the stimulation of motor cortex and utilizing motor evoked potentials as direct readout. However, knowledge of immediate DLPFC modulation by TBS is necessary to extrapolate downstream effects on the neural and symptoms level.
Thus, there is a need for research that aims to quantify the direct and immediate after-effects of TBS on DLPFC function. Most importantly, with regard to precision medicine, there is a need for research that explores the utility of immediate DLPFC reactivity to TBS for the prediction of antidepressant treatment response. There is common agreement that certain forms of rTMS inhibit or excite brain activity, respectively. However, evidence indicates that there is considerable individual variability in the brain responses to rTMS. Whether differences in individual DLPFC modulation by rTMS can be utilized as a predictive marker for treatment response remains to be investigated.
Read more
This research program will exploit the combination of functional near-infrared spectroscopy (fNIRS) with brain stimulation. Concurrent TBS/fNIRS measurements will allow us to systematically investigate TBS-induced modulation of blood oxygenation as a proxy for induced brain activity changes. The findings from this study will (1) elucidate the immediate effects of excitatory and inhibitory TBS on prefrontal activity in TBS treatment-naïve patients with MDD and (2) validate the potential utility of TBS-induced brain modulation at baseline for the prediction of antidepressant response to four weeks of daily TBS treatment.
Major depression is a severe mental disorder and is associated with considerable economic costs but adequate treatments are poorly explored. This research program will pave the way towards an affordable and easy-to-implement method for response prediction before treatment commencement. Thus, our research proposal has high potential to inform tailored treatment strategies, as envisaged in precision medicine.
Read the detailed description
Please refer to the full proposal
- Conditions
- Major Depressive Disorder
- Being tested
- Theta-burst stimulation (TBS)
- Keywords
- Theta-Burst Stimulation, Major depression, Treatment prediction, Functional NIRS, Concurrent TBS/fNIRS
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Theta-burst stimulation (TBS)Device
Also called Transcranial Magnetic Stimulation
TBS comprises 3-pulse 50-Hz bursts, applied every 200 ms (at 5 Hz) as described previously (Huang, Edwards et al. 2005). iTBS consists of 2-second trains with an inter-train-interval of 8 seconds. We will repeat trains (30 pulses; 10 bursts) for 20 times to reach a total number of 600 pulses (3x10x20). cTBS will comprise uninterrupted bursts to reach a total number of 600 pulses, as done routinely by others. Concurrent TBS/fNIRS stimulation will be applied over the left (iTBS) and right (cTBS) DLPFC at an intensity of 70-120%* resting motor threshold (RMT) (The ideal %RMT will be determined first in a pilot study). In part two, stimulation intensity for patients will be 120% RMT (titration to full therapeutic dose over the first three days), as approved by the FDA in the U.S. (Blumbeger et al. 2018). The stimulation site will be the same as in the concurrent TBS/fNIRS stimulation (see above).
| Study group | Role | What they receive |
|---|---|---|
| Concurrent TBS/fNIRS with iTBS and followed by cTBS after 1h | Experimental | self-explanatory, see Arm Title Receives: Device: Theta-burst stimulation (TBS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate after treatment (Montgomery-Asberg depression rating scale, MADRS reduction ≥50% of baseline)
We will use the MADRS as the primary outcome measure because this symptom rating scale is more sensitive to changes over time. The score of MADRS is ranging from 0 to 60, with higher scores indicative of greater depressive symptomology.
Measured: post treatment, up to 22 months
Oxygenated hemoglobin (HbO) change compared to baseline
TBS-induced HbO change in the DLPFC during and after stimulation
Measured: during and post TBS-fNIRS measurement, an average of 2 months. As well as at follow-up, up to 30 months
Secondary outcomes (6)
Remission rate after treatment (MADRS≤10)
See above
Measured: post treatment, up to 22 months
Absolute change of mean Hamilton depression rating scale (HAMD17) after 2 and 4 weeks of treatment, as well as at 1 month follow-up
The score of HAMD is ranging from 0 to 53, on which increasing scores represent increasing severity of symptoms
Measured: at follow-up, up to 30 months
Absolute change of mean Inventory of depression symptomatology-clinician (IDS-C30) after 2 and 4 weeks of treatment, as well as at 1 month follow-up
The score of IDS-C30 ranges from 0 to 84, on which increasing scores represent increasing severity of symptoms
Measured: at follow-up, up to 30 months
Hb change compared to baseline
TBS-induced Hb change in the DLPFC during and after stimulation
Measured: during and post TBS-fNIRS measurement, an average of 2 months. As well as at follow-up, up to 30 months
the area under curve of HbO and Hb value during stimulation
TBS-induced HbO and Hb change in the DLPFC during stimulation
Measured: during TBS-fNIRS measurement, an average of 2 months. As well as at follow-up, up to 30 months
the steepness of the Hb and HbO values change
TBS-induced HbO and Hb change in the DLPFC during stimulation
Measured: during TBS-fNIRS measurement, an average of 2 months. As well as at follow-up, up to 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2020
- Study start1 Mar 2023
- Primary completion15 May 2024
- Study completion15 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Patients with MDD and healthy controls will undergo TBS/fNIRS to investigate the direct effects of TBS of healthy and presumed neuropathological prefrontal cortex. This is followed by a 4-week TBS treatment for MDD patients in order to evaluate the relationship between immediate excitability modulations of the DLPFC and treatment response.
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr Georg Kranz
- Sponsor type
- University, hospital or other
- Collaborators
- Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, Kowloon Hospital, Hong Kong
- Responsible party
- Sponsor-investigator, Dr Georg Kranz, The Hong Kong Polytechnic University
- Investigators
- Georg S Kranz, PhD, Principal investigator, The Hong Kong Polytechnic University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04526002
- Sponsor's protocol ID
- 15100120
- Status last verified
- Mar 2024
- First submitted
- 19 Aug 2020
- Last updated
- 13 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kan RLD, Mak ADP, Chan SKW, Zhang BBB, Fong KNK, Kranz GS. Protocol for a prospective open-label clinical trial to investigate the utility of concurrent TBS/fNIRS for antidepressant treatment optimisation. BMJ Open. 2022 Feb 10;12(2):e053896. doi: 10.1136/bmjopen-2021-053896.
PubMed 35144953
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Utility of Concurrent TBS/fNIRS for Antidepressant Treatment Optimization
- ClinicalTrials.gov ID
- NCT04526002
- Acronym / sponsor ID
- 15100120
- Conditions
- Major Depressive Disorder
- Keywords
- Theta-Burst Stimulation, Major depression, Treatment prediction, Functional NIRS, Concurrent TBS/fNIRS
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Dr Georg KranzUniversity, hospital or other
- Collaborators
- Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, Kowloon Hospital, Hong Kong
- Study start
- 1 Mar 2023 (actual)
- Primary completion
- 15 May 2024 (actual)
- Study completion
- 15 May 2024 (actual)
- First posted
- 25 Aug 2020 (actual)
- 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.
Repetitive transcranial magnetic stimulation (rTMS) with theta bursts (i.e. TBS) of the dorsolateral prefrontal cortex (DLPFC) is an innovative treatment for major depressive disorder (MDD). Indeed, the U. S. Food and Drug Administration (FDA) has only recently approved TBS (in August 2018). However, fewer than 50% of patients show sufficient response to this treatment; markers for response prediction are urgently needed. Moreover, there is a lack of knowledge of the mechanism of action of TBS of the DLPFC. This is due to difficulties of directly measuring prefrontal stimulation effects, as compared to the stimulation of motor cortex and utilizing motor evoked potentials as direct readout. However, knowledge of immediate DLPFC modulation by TBS is necessary to extrapolate downstream effects on the neural and symptoms level.
Thus, there is a need for research that aims to quantify the direct and immediate after-effects of TBS on DLPFC function. Most importantly, with regard to precision medicine, there is a need for research that explores the utility of immediate DLPFC reactivity to TBS for the prediction of antidepressant treatment response. There is common agreement that certain forms of rTMS inhibit or excite brain activity, respectively. However, evidence indicates that there is considerable individual variability in the brain responses to rTMS. Whether differences in individual DLPFC modulation by rTMS can be utilized as a predictive marker for treatment response remains to be investigated.
This research program will exploit the combination of functional near-infrared spectroscopy (fNIRS) with brain stimulation. Concurrent TBS/fNIRS measurements will allow us to systematically investigate TBS-induced modulation of blood oxygenation as a proxy for induced brain activity changes. The findings from this study will (1) elucidate the immediate effects of excitatory and inhibitory TBS on prefrontal activity in TBS treatment-naïve patients with MDD and (2) validate the potential utility of TBS-induced brain modulation at baseline for the prediction of antidepressant response to four weeks of daily TBS treatment.
Major depression is a severe mental disorder and is associated with considerable economic costs but adequate treatments are poorly explored. This research program will pave the way towards an affordable and easy-to-implement method for response prediction before treatment commencement. Thus, our research proposal has high potential to inform tailored treatment strategies, as envisaged in precision medicine.
Detailed description
Please refer to the full proposal
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients with MDD and healthy controls will undergo TBS/fNIRS to investigate the direct effects of TBS of healthy and presumed neuropathological prefrontal cortex. This is followed by a 4-week TBS treatment for MDD patients in order to evaluate the relationship between immediate excitability modulations of the DLPFC and treatment response.
| Arm | Type | Receives |
|---|---|---|
| Concurrent TBS/fNIRS with iTBS and followed by cTBS after 1h | Experimental | Device: Theta-burst stimulation (TBS)self-explanatory, see Arm Title |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- MDD (DSM-5), HAMD17 ≥18, approval for TBS treatment by the physician in charge, stable antidepressive medication 4 weeks before treatment (the sample will include at least 20 drug-naïve patients in order to avoid confounding effects of medication for testing hypothesis 4).
- age between 18 and 60, right-handedness.
Key exclusion criteria (3 listed)
- a history of brain surgery, head injury, stroke or neurodegenerative disorder, diagnosis of personality disorder, psychotic features, active suicidal intent, severe somatic comorbidities, cardiac pacemakers, deep brain stimulation, intracranial metallic particles, history of seizures, antiepileptics and benzodiazepines corresponding to a dose of >1 mg lorazepam/d, substance dependence or abuse, if it is the primary clinical problem.
- a current or previous diagnosis of a psychiatric, neurological disorder or severe internal illness, common contraindications to rTMS,26 and a psychiatric disorder in their first-degree relatives.
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 (TBS)Also: Transcranial Magnetic StimulationTBS comprises 3-pulse 50-Hz bursts, applied every 200 ms (at 5 Hz) as described previously (Huang, Edwards et al. 2005). iTBS consists of 2-second trains with an inter-train-interval of 8 seconds. We will repeat trains (30 pulses; 10 bursts) for 20 times to reach a total number of 600 pulses (3x10x20). cTBS will comprise uninterrupted bursts to reach a total number of 600 pulses, as done routinely by others. Concurrent TBS/fNIRS stimulation will be applied over the left (iTBS) and right (cTBS) DLPFC at an intensity of 70-120%* resting motor threshold (RMT) (The ideal %RMT will be determined first in a pilot study). In part two, stimulation intensity for patients will be 120% RMT (titration to full therapeutic dose over the first three days), as approved by the FDA in the U.S. (Blumbeger et al. 2018). The stimulation site will be the same as in the concurrent TBS/fNIRS stimulation (see above). | Device | Concurrent TBS/fNIRS with iTBS and followed by cTBS after 1h |
Primary outcome
Response rate after treatment (Montgomery-Asberg depression rating scale, MADRS reduction ≥50% of baseline)
Time frame: post treatment, up to 22 months
We will use the MADRS as the primary outcome measure because this symptom rating scale is more sensitive to changes over time. The score of MADRS is ranging from 0 to 60, with higher scores indicative of greater depressive symptomology.
Oxygenated hemoglobin (HbO) change compared to baseline
Time frame: during and post TBS-fNIRS measurement, an average of 2 months. As well as at follow-up, up to 30 months
TBS-induced HbO change in the DLPFC during and after stimulation
6 secondary outcomes
Remission rate after treatment (MADRS≤10)
Time frame: post treatment, up to 22 months
Absolute change of mean Hamilton depression rating scale (HAMD17) after 2 and 4 weeks of treatment, as well as at 1 month follow-up
Time frame: at follow-up, up to 30 months
Absolute change of mean Inventory of depression symptomatology-clinician (IDS-C30) after 2 and 4 weeks of treatment, as well as at 1 month follow-up
Time frame: at follow-up, up to 30 months
Hb change compared to baseline
Time frame: during and post TBS-fNIRS measurement, an average of 2 months. As well as at follow-up, up to 30 months
the area under curve of HbO and Hb value during stimulation
Time frame: during TBS-fNIRS measurement, an average of 2 months. As well as at follow-up, up to 30 months
the steepness of the Hb and HbO values change
Time frame: during TBS-fNIRS measurement, an average of 2 months. As well as at follow-up, up to 30 months
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 13 Apr 2025.
- Derived from this study: PubMed 35144953Kan RLD, Mak ADP, Chan SKW, Zhang BBB, Fong KNK, Kranz GS. Protocol for a prospective open-label clinical trial to investigate the utility of concurrent TBS/fNIRS for antidepressant treatment optimisation. BMJ Open. 2022 Feb 10;12(2):e053896. doi: 10.1136/bmjopen-2021-053896.
- Individual participant dataSharing planned: No
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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.
Georg S Kranz, PhD principal investigator
The Hong Kong Polytechnic University
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 (TBS) in people with Major Depressive Disorder, run by Dr Georg Kranz at 1 site in Hong Kong.
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 2 inclusion and 3 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: finished, as of the sponsor's last update on 13 Apr 2025. 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 Hong Kong. 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?
Response rate after treatment (Montgomery-Asberg depression rating scale, MADRS reduction ≥50% of baseline) (time frame: post treatment, up to 22 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04526002, which also lists 1 linked publication.
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 13 Apr 2025.