The Utility of Concurrent TBS/fNIRS for Antidepressant Treatment Optimization

NCT04526002 | Completed

• 1 other identifier: 15100120
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder

Keywords

Theta-Burst Stimulation; Major depression; Treatment prediction; Functional NIRS; Concurrent TBS/fNIRS

Outcome Measures

Primary Outcomes (2)

• 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.

  post treatment, up to 22 months

• Oxygenated hemoglobin (HbO) change compared to baseline

  TBS-induced HbO change in the DLPFC during and after stimulation

  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)

  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

  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

  at follow-up, up to 30 months

• Hb change compared to baseline

  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

  during TBS-fNIRS measurement, an average of 2 months. As well as at follow-up, up to 30 months

Other Outcomes (1)

• Change of Patient Health Questionnaire (PHQ-9, Chinese version) at each treatment day

  till to end of treatment, up to 18 months

Study Arms (1)

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

EXPERIMENTAL

self-explanatory, see Arm Title

Device: Theta-burst stimulation (TBS)

Interventions

Theta-burst stimulation (TBS) 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).

Also known as: Transcranial Magnetic Stimulation

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

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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:
• age between 18 and 60, right-handedness.
• 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.

Sponsors & Collaborators

• Dr Georg Kranz: lead
• Chinese University of Hong Kong: collaborator
• Prince of Wales Hospital, Shatin, Hong Kong: collaborator
• Kowloon Hospital, Hong Kong: collaborator

Study Sites (1)

The Hong Kong Polytechnic University

Hong Kong, Hong Kong

Location

Related Publications (1)

• 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.

  PMID: 35144953 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Georg S Kranz, PhD

  The Hong Kong Polytechnic University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: August 19, 2020
• First Posted: August 25, 2020
• Study Start: March 1, 2023
• Primary Completion: May 15, 2024
• Study Completion: May 15, 2024
• Last Updated: April 13, 2025

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)