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NCT Number: NCT07474974

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.

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Key information

Conditions

Depression - Major Depressive Disorder Depressive Disorder Depressive Disorder, Major Depressive Disorder, Treatment-Resistant Mental Disorders Mood Disorders Treatment Resistant Depression

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Repetitive transcranial magnetic stimulation (rTMS)

Device

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: Active rTMS, DLPFC rTMS, Active iTBS, iTBS

Primary outcomes

  1. 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

Secondary outcomes

  1. 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)

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Catarina C Mateus, PhD

CONTACT

[email protected]

+351 962662157

Inês Duarte D Pais, MSc

CONTACT

[email protected]

+351 917750656

Sponsors and collaborators

Lead sponsor

Polytechnic Institute of Porto

Other

Collaborators

  • Hospital de Sao Joao, Porto

Registry information

Official study title

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

Acronym: BRIGHT

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Mar 16, 2026
Registry last updated
Mar 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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