ipRGC as a Potential Biomarker for Predicting Transcranial Magnetic Stimulation Treatment Response in Major Depressive Disorder (BRIGHT)

March 11, 2026 updated by: Catarina Mateus, PhD, Polytechnic Institute of Porto

Illuminating Depression: ipRGC as a Potential Biomarker for Predicting Transcranial Magnetic Stimulation Treatment Response in Major Depressive Disorder

This research explores the potential of retinal ganglion cells (RGCs), particularly intrinsically photosensitive RGCs (ipRGCs), as biomarkers for predicting response to transcranial magnetic stimulation (TMS) in treatment-resistant depression (TRD). We also aim to assess the impact of TMS treatment on RGCs and ipRGCs in TRD patients, investigating associations with clinical improvements and cognitive status. A clinical trial involving 44 patients with treatment-resistant depression (TRD) will be conducted. All participants will receive rTMS targeting the dorsolateral prefrontal cortex (DLPFC). Data will be collected pre- and post-intervention, as well as at a 2-month follow-up, using multiple outcome measures, including the post-illumination pupil response (PIPR). The project seeks to confirm the effectiveness of TMS and the potential of RGCs/ipRGCs as predictors of treatment response, thereby facilitating the development of personalized treatment strategies for TRD patients undergoing rTMS therapy.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

44

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Inês Duarte D Pais, MSc
  • Phone Number: +351 917750656
  • Email: idp@ess.ipp.pt

Study Contact Backup

  • Name: Catarina C Mateus, PhD
  • Phone Number: +351 962662157
  • Email: cms@ess.ipp.pt

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of MDD, confirmed via the structured clinical interview;
  • TRD type;
  • Age between 18-65 years;
  • Visual acuity of 20/32 or better.

Exclusion Criteria:

  • Prior rTMS treatment;
  • Contraindications for TMS;
  • Psychiatric disorders other than MDD;
  • Systemic diseases affecting the eyes (e.g., diabetes mellitus);
  • Ocular conditions;
  • Head injuries causing loss of consciousness;
  • Current or past alcohol/substance dependence within 6 months;
  • Neurodegenerative diseases;
  • Major neurological illnesses;
  • Use of medications affecting iris mechanics or the autonomic nervous system.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: iTBS
iTBS Group (n=44) will receive high-frequency (50 Hz) left-side DLPFC iTBS (120% RMT stimulation intensity; 50 Hz frequency; 2s on and 8 s off; 600 pulses/session; total duration of 3 minutes). Treatment comprised 20 sessions in total, which consisted of once-daily sessions (on weekdays).
Device: Repetitive transcranial magnetic stimulation (rTMS)
Each participant's resting motor threshold (RMT) will be determined by visual observation in accordance with standard clinical practice. Intermittent theta-burst stimulation (iTBS) will be delivered over the left dorsolateral prefrontal cortex (DLPFC) using these parameters: stimulation intensity 120% RMT; bursts at 50 Hz; 2 s on and 8 s off; 600 pulses per session; total stimulation time approximately 3 minutes per session. Stimulation will be delivered using a MagPro X100 stimulator with MagOption, equipped with a B70 butterfly-shaped coil with static cooling (MagVenture, Denmark). Treatment will comprise 20 sessions, delivered once daily on weekdays.
Other Names:
  • iTBS
  • Active rTMS
  • Active iTBS
  • DLPFC rTMS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Chromatic pupillometry
Time Frame: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
To extract post-illumination pupil response (PIPR) derived from ipRGCs
Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Optical Coherence Tomography (OCT)
Time Frame: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
To extract central retinal thickness and thicknesses of retina neuronal layers (GCL-IPL and RNFL)
Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
Pattern Electroretinogram (PERG)
Time Frame: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
To extract PERG N95 wave related to RGC function.
Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
Contrast sensitivity test
Time Frame: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
To measure contrast sensitivity
Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
Montgomery-Åsberg Depression Rating Scale (MADRS)
Time Frame: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
To evaluate treatment response. Scores range from 0 to 60, with higher scores indicating more severe depressive symptoms.
Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
Maudsley Staging Depression
Time Frame: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
To assess the level of treatment resistance in depression. Scores range from 3 to 15, with higher scores indicating greater treatment resistance.
Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
California Verbal Learning Test-II (CVLT-II)
Time Frame: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
To assess verbal learning and memory. Scores range from 0 to 80, with higher scores indicating better verbal learning and memory performance.
Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
Reading Mind in Eyes Test (RMET)
Time Frame: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
To assess social cognition and theory of mind through recognition of mental states from images of the eye region. Scores range from 0 to 36, with higher scores indicating better social cognitive performance.
Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
Symbol Digit Modalities Test (SDMT)
Time Frame: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
To assess information processing speed and attention. Scores range from 0 to 110, with higher scores indicating better cognitive processing speed performance.
Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
Brief Visuospatial Memory Test-Revised (BVMT-R)
Time Frame: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
To assess visuospatial learning and memory. Scores range from 0 to 36, with higher scores indicating better visuospatial memory performance.
Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
WHODAS 12-item (Self-report)
Time Frame: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)
To assess disability and functional impairment in daily life. Scores range from 12 to 60, with higher scores indicating greater disability.
Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Polytechnic Institute of Porto

Collaborators

Hospital de Sao Joao, Porto

Investigators

  • Study Director: Catarina C Mateus, PhD, Polytechnic Institute of Porto

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 15, 2026

Primary Completion (Estimated)

April 30, 2027

Study Completion (Estimated)

July 31, 2027

Study Registration Dates

First Submitted

March 6, 2026

First Submitted That Met QC Criteria

March 11, 2026

First Posted (Actual)

March 16, 2026

Study Record Updates

Last Update Posted (Actual)

March 16, 2026

Last Update Submitted That Met QC Criteria

March 11, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ORT-2026-001
  • 2024.06665.BD (Other Grant/Funding Number: Foundation for Science and Technology (FCT), Portugal)
  • CE0085E (Other Identifier: Ethics Committee of the School of Health of the Polytechnic Institute of Porto)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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