Major Depression in RemissionTBS/fNIRSNCT05579015
Predicting Illness Trajectories In Fully Remitted Major Depression Using Concurrent TBS/fNIRS
A study testing Theta-burst stimulation (TBS) and telephone interviews in people with Major Depression in Remission and Healthy, run by The Hong Kong Polytechnic University at 1 site in China.
Trial summary
Major depressive disorder (MDD) is the world's leading cause of disability according to the World Health Organization. MDD is highly recurrent, even if clinical remission is reached after successful treatment. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depression in Remission, Healthy
- What is being tested?
- Theta-burst stimulation (TBS) and telephone interviews
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 170 participants
- Where
- 1 siteChina
- Study dates
- 8 Oct 2023to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- a clinical diagnosis of recurrent depressive disorder by an experienced psychiatrist but currently in full remission (ICD 11, 6A71.7) according to results of the Mini International Neuropsychiatric Interview (MINI) and the Patient Health Questionnaire (PHQ-9), with a score ≤ 4;
- at least two previous MDEs within the last 10 years;
- no or stable (≥4 weeks) psychopharmacological medication.
Who cannot join
- severe internal diseases;
- neurological disorders or a history of severe head injuries;
- current psychiatric comorbidities, including addiction;
- pregnancy;
- common fNIRS and TMS exclusion criteria, such as a history of brain surgery, head injury, cardiac pacemaker, deep brain stimulation, intracranial metallic particles, history of seizures, and antiepileptics and benzodiazepines corresponding to a dose of >1 mg lorazepam/d. Potential participants taking antidepressants will be included if there has been no recent change to either dosage or medication (within 4 weeks).
Trial locations and contacts
1 site in 1 country.
About this study
Major depressive disorder (MDD) is the world's leading cause of disability according to the World Health Organization. MDD is highly recurrent, even if clinical remission is reached after successful treatment. In fact, the enormous burden of disability, mortality and financial costs is due to the recurrent and chronic nature of MDD. The reliable prediction of the recurrence of major depressive episodes (MDEs) based on a prognostic model that is informed by biological, neurophysiological or neuroimaging data would be valuable and lifesaving for many. However, such models are still lacking.
Several lines of evidence point to abnormal prefrontal control over limbic emotion processing areas in MDD owing to diminished prefrontal excitability that seems to persist during MDD remission (rMDD). Prefrontal excitability in rMDD may thus be a trait marker of MDD and may potentially be indicative of disease recurrence. Yet, research investigating the potential utility of prefrontal excitability for predicting the recurrence of MDEs is lacking. Cortical excitability can be investigated using transcranial magnetic stimulation (TMS); however, human studies have mostly probed cortical excitability of the motor cortex, a brain region not considered to be central in the neuropathology of MDD. Hence, knowledge of the effect of TMS on prefrontal excitability is limited. Moreover, whether immediate prefrontal modulation by TMS can predict the recurrence of MDEs in fully remitted MDD patients remains to be investigated. Thus, there is a need for research that aims to quantify the direct and immediate aftereffects of TMS on prefrontal function. Most importantly, with regard to precision medicine, there is a need for research that explores the utility of immediate prefrontal reactivity to TMS for predicting MDE recurrence. Here, the investigators propose a research program that will exploit the combination of functional near-infrared spectroscopy (fNIRS) with brain stimulation. Concurrent theta-burst stimulation (TBS)/fNIRS measurements will allow us to systematically investigate stimulation-induced modulation of blood oxygenation as a proxy for induced brain activity changes (TBS is a modern form of patterned TMS). The findings from this study will (1) elucidate the immediate effects of excitatory and inhibitory brain stimulation on prefrontal activity in rMDD and controls and (2) validate the potential utility of stimulation-induced brain modulation for the prediction of MDE recurrence.
- Conditions
- Major Depression in Remission, Healthy
- Being tested
- Theta-burst stimulation (TBS), telephone interviews
- Keywords
- Theta-burst stimulation, Remitted depression, Relapse prediction, Functional NIRS, Concurrent TBS/fNIRS
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 Repetitive transcranial magnetic stimulation (rTMS)
TBS comprises 3-pulse 50-Hz bursts, applied every 200 ms (at 5 Hz), as described previously. iTBS consists of 2-second trains with an inter-train interval of 8 seconds. The investigators will repeat the trains (30 pulses; 10 bursts) 20 times to reach a total number of 600 pulses (3x10x20). cTBS will comprise uninterrupted bursts to reach a total of 600 pulses. Concurrent TBS/fNIRS stimulation will be applied over the left (iTBS) and right (cTBS) DLPFC at an intensity of 90% resting motor threshold (RMT). This corresponds to ~110% of the active motor threshold. Stimulation at 90% RMT will also ensure compliance, reduce sensory discomfort and minimize dropout rates. Still, scalp discomfort will be recorded directly after the stimulation. The stimulation site over the DLPFC will be determined using the international 10-20 system and correspond to the F3 label.
telephone interviewsOther
Telephone interviews will be conducted at the follow-up stage. RMDD group will receive follow-up telephone interviews every 3 months for 2 years to monitor major depressive episode recurrence
| Study group | Role | What they receive |
|---|---|---|
| rMDD group | Experimental | Participants with remitted MDD who will receive concurrent TBS/fNIRS with iTBS and followed by cTBS after one hour. This group will also receive follow-up telephone interviews every 3 months for 2 years to monitor major depressive episode recurrence. Receives: Device: Theta-burst stimulation (TBS); Other: telephone interviews |
| Healthy control group | Other | Healthy participants who will receive TBS/fNIRS with iTBS and followed by cTBS after one hour. No follow-up interviews will be conducted for this group. Receives: Device: Theta-burst stimulation (TBS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence of a major depressive episode
Primary clinical outcome measure: recurrence of a major depressive episode (based on MINI and PhQ-9 ≥ 5).
Measured: Up to 2 years.
Oxyhemoglobin (HbO) change compared to baseline
Primary imaging outcome measure: TBS-induced HbO change in the dorsolateral prefrontal cortex (DLPFC) during and after stimulation.
Measured: During and within 3 minutes post TBS-fNIRS measurement.
Secondary outcomes (1)
Hemoglobin (Hb) change compared to baseline
Secondary Imaging Outcome Measure: TBS-induced Hemoglobin (Hb) change in the dorsolateral prefrontal cortex (DLPFC) during and after stimulation
Measured: During and within 3 minutes post TBS-fNIRS measurement
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2022
- Study start8 Oct 2023
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depression in RemissionStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 170 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Hong Kong Polytechnic University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Georg Kranz, The Hong Kong Polytechnic University
- Investigators
- Georg S. Kranz, PhD, Principal investigator, The Kong Kong Polytechnic University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05579015
- Sponsor's protocol ID
- HSEARS20220812002
- Acronym
- TBS/fNIRS
- Status last verified
- Sep 2025
- First submitted
- 14 Sep 2022
- Last updated
- 11 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD may be shared upon request
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predicting Illness Trajectories In Fully Remitted Major Depression Using Concurrent TBS/fNIRS
- ClinicalTrials.gov ID
- NCT05579015
- Acronym / sponsor ID
- TBS/fNIRS / HSEARS20220812002
- Conditions
- Major Depression in Remission, Healthy
- Keywords
- Theta-burst stimulation, Remitted depression, Relapse prediction, Functional NIRS, Concurrent TBS/fNIRS
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 170 participants (estimated)
- Lead sponsor
- The Hong Kong Polytechnic UniversityUniversity, hospital or other
- Study start
- 8 Oct 2023 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 13 Oct 2022 (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.
Major depressive disorder (MDD) is the world's leading cause of disability according to the World Health Organization. MDD is highly recurrent, even if clinical remission is reached after successful treatment. In fact, the enormous burden of disability, mortality and financial costs is due to the recurrent and chronic nature of MDD. The reliable prediction of the recurrence of major depressive episodes (MDEs) based on a prognostic model that is informed by biological, neurophysiological or neuroimaging data would be valuable and lifesaving for many. However, such models are still lacking.
Several lines of evidence point to abnormal prefrontal control over limbic emotion processing areas in MDD owing to diminished prefrontal excitability that seems to persist during MDD remission (rMDD). Prefrontal excitability in rMDD may thus be a trait marker of MDD and may potentially be indicative of disease recurrence. Yet, research investigating the potential utility of prefrontal excitability for predicting the recurrence of MDEs is lacking. Cortical excitability can be investigated using transcranial magnetic stimulation (TMS); however, human studies have mostly probed cortical excitability of the motor cortex, a brain region not considered to be central in the neuropathology of MDD. Hence, knowledge of the effect of TMS on prefrontal excitability is limited. Moreover, whether immediate prefrontal modulation by TMS can predict the recurrence of MDEs in fully remitted MDD patients remains to be investigated. Thus, there is a need for research that aims to quantify the direct and immediate aftereffects of TMS on prefrontal function. Most importantly, with regard to precision medicine, there is a need for research that explores the utility of immediate prefrontal reactivity to TMS for predicting MDE recurrence. Here, the investigators propose a research program that will exploit the combination of functional near-infrared spectroscopy (fNIRS) with brain stimulation. Concurrent theta-burst stimulation (TBS)/fNIRS measurements will allow us to systematically investigate stimulation-induced modulation of blood oxygenation as a proxy for induced brain activity changes (TBS is a modern form of patterned TMS). The findings from this study will (1) elucidate the immediate effects of excitatory and inhibitory brain stimulation on prefrontal activity in rMDD and controls and (2) validate the potential utility of stimulation-induced brain modulation for the prediction of MDE recurrence.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| rMDD group | Experimental | Device: Theta-burst stimulation (TBS), Other: telephone interviewsParticipants with remitted MDD who will receive concurrent TBS/fNIRS with iTBS and followed by cTBS after one hour. This group will also receive follow-up telephone interviews every 3 months for 2 years to monitor major depressive episode recurrence. |
| Healthy control group | Other | Device: Theta-burst stimulation (TBS)Healthy participants who will receive TBS/fNIRS with iTBS and followed by cTBS after one hour. No follow-up interviews will be conducted for this group. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- a clinical diagnosis of recurrent depressive disorder by an experienced psychiatrist but currently in full remission (ICD 11, 6A71.7) according to results of the Mini International Neuropsychiatric Interview (MINI) and the Patient Health Questionnaire (PHQ-9), with a score ≤ 4;
- at least two previous MDEs within the last 10 years;
- no or stable (≥4 weeks) psychopharmacological medication.
Key exclusion criteria (5 listed)
- severe internal diseases;
- neurological disorders or a history of severe head injuries;
- current psychiatric comorbidities, including addiction;
- pregnancy;
- common fNIRS and TMS exclusion criteria, such as a history of brain surgery, head injury, cardiac pacemaker, deep brain stimulation, intracranial metallic particles, history of seizures, and antiepileptics and benzodiazepines corresponding to a dose of >1 mg lorazepam/d. Potential participants taking antidepressants will be included if there has been no recent change to either dosage or medication (within 4 weeks).
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: Repetitive transcranial magnetic stimulation (rTMS)TBS comprises 3-pulse 50-Hz bursts, applied every 200 ms (at 5 Hz), as described previously. iTBS consists of 2-second trains with an inter-train interval of 8 seconds. The investigators will repeat the trains (30 pulses; 10 bursts) 20 times to reach a total number of 600 pulses (3x10x20). cTBS will comprise uninterrupted bursts to reach a total of 600 pulses. Concurrent TBS/fNIRS stimulation will be applied over the left (iTBS) and right (cTBS) DLPFC at an intensity of 90% resting motor threshold (RMT). This corresponds to ~110% of the active motor threshold. Stimulation at 90% RMT will also ensure compliance, reduce sensory discomfort and minimize dropout rates. Still, scalp discomfort will be recorded directly after the stimulation. The stimulation site over the DLPFC will be determined using the international 10-20 system and correspond to the F3 label. | Device | Healthy control group, rMDD group |
| telephone interviewsTelephone interviews will be conducted at the follow-up stage. RMDD group will receive follow-up telephone interviews every 3 months for 2 years to monitor major depressive episode recurrence | Other | rMDD group |
Primary outcome
Recurrence of a major depressive episode
Time frame: Up to 2 years.
Primary clinical outcome measure: recurrence of a major depressive episode (based on MINI and PhQ-9 ≥ 5).
Oxyhemoglobin (HbO) change compared to baseline
Time frame: During and within 3 minutes post TBS-fNIRS measurement.
Primary imaging outcome measure: TBS-induced HbO change in the dorsolateral prefrontal cortex (DLPFC) during and after stimulation.
1 secondary outcome
Hemoglobin (Hb) change compared to baseline
Time frame: During and within 3 minutes post TBS-fNIRS measurement
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2025.
- Individual participant dataSharing planned: Yes. IPD may be shared upon request
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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 Kong 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) and telephone interviews in people with Major Depression in Remission and Healthy, run by The Hong Kong Polytechnic University at 1 site in China.
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 3 inclusion and 5 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: under way, not looking for participants, as of the sponsor's last update on 11 Sep 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 China. 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?
This study is still under way. Results are not available in the source record yet.
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?
Recurrence of a major depressive episode (time frame: Up to 2 years.). 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?
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 11 Sep 2025.