Predicting Illness Trajectories In Fully Remitted Major Depression Using Concurrent TBS/fNIRS

NCT05579015 | Active Not Recruiting

• 1 other identifier: HSEARS20220812002
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

Brief 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. 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

Keywords

Theta-burst stimulation; Remitted depression; Relapse prediction; Functional NIRS; Concurrent TBS/fNIRS

Outcome Measures

Primary Outcomes (2)

• Recurrence of a major depressive episode

  Primary clinical outcome measure: recurrence of a major depressive episode (based on MINI and PhQ-9 ≥ 5).

  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.

  During and within 3 minutes post TBS-fNIRS measurement.

Secondary Outcomes (1)

• Hemoglobin (Hb) change compared to baseline

  During and within 3 minutes post TBS-fNIRS measurement

Study Arms (2)

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.

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.

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. 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.

Also known as: Repetitive transcranial magnetic stimulation (rTMS)

Healthy control group; rMDD group

telephone interviews OTHER

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

rMDD group

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• severe internal diseases;
• neurological disorders or a history of severe head injuries;
• current psychiatric comorbidities, including addiction;
• pregnancy;

Sponsors & Collaborators

• The Hong Kong Polytechnic University: lead

Study Sites (1)

The Hong Kong Polytechnic University

Hong Kong, China

Location

MeSH Terms

Interventions

Transcranial Magnetic Stimulation; Interviews as Topic

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Georg S. Kranz, PhD

  The Kong Kong Polytechnic University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 14, 2022
• First Posted: October 13, 2022
• Study Start: October 8, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Upon request
• Access Criteria: Upon request

Locations

CN (1)