The Utility of Concurrent TBS/fNIRS for Antidepressant Treatment Optimization

NCT ID: NCT04526002

Last Updated: 2025-04-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-01
• Study Completion Date: 2024-05-15

Brief 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). 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

Conditions

Major Depressive Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Concurrent TBS/fNIRS with iTBS and followed by cTBS after 1h

self-explanatory, see Arm Title

Group Type: EXPERIMENTAL

Theta-burst stimulation (TBS)

Intervention Type: DEVICE

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).

Interventions

Theta-burst stimulation (TBS)

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).

Intervention Type: DEVICE

Other Intervention Names

Transcranial Magnetic Stimulation

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: collaborator

Prince of Wales Hospital, Shatin, Hong Kong

OTHER

Sponsor Role: collaborator

Kowloon Hospital, Hong Kong

OTHER

Sponsor Role: collaborator

Dr Georg Kranz

OTHER

Sponsor Role: lead

Responsible Party

Dr Georg Kranz

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Georg S Kranz, PhD

Role: PRINCIPAL_INVESTIGATOR

The Hong Kong Polytechnic University

Locations

The Hong Kong Polytechnic University

Hong Kong, , Hong Kong

Countries

Hong Kong

References

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.

Reference Type: DERIVED

PMID: 35144953 (View on PubMed)

Other Identifiers

15100120

Identifier Type: -

Identifier Source: org_study_id