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Depression - Major Depressive DisorderBRIGHTNCT07474974

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

A study testing Repetitive transcranial magnetic stimulation (rTMS) in people with Depression - Major Depressive Disorder and Treatment Resistant Depression, run by Polytechnic Institute of Porto at 1 site in Portugal.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Repetitive transcranial magnetic stimulation (rTMS)
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
44 participants
Where
1 sitePortugal
Study dates
15 Mar 2026to 31 Jul 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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;
Show all 10Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Inês Duarte D Pais, MSc contact

+351 222 061 000

idp@ess.ipp.pt

Catarina C Mateus, PhD contact

+351 222 061 000

cms@ess.ipp.pt

Portugal1 site, 1 recruiting

  • RISE-Health, Center for Translational Health and Medical Biotechnology Research (TBIO), School of Health, Polytechnic of Porto

    Porto, Porto District, 4200-072

    Nuno B Rocha, PhD, +351 913474780, nrocha@ess.ipp.pt

    Recruiting

Other trials in Portugal

About this study

Official title: 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.

Being tested
Repetitive transcranial magnetic stimulation (rTMS)
Keywords
Major Depressive Disorder, Repetitive Transcranial Magnetic Stimulation, Retinal Ganglion Cells, ipRGCs, Treatment-resistant depression
Medical subject headings
Depressive Disorder, Treatment-Resistant, Depressive Disorder, Major

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Repetitive transcranial magnetic stimulation (rTMS)Device

    Also called Active rTMS, DLPFC rTMS, Active iTBS, iTBS

    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.

Study groups in NCT07474974
Study groupRoleWhat they receive
iTBSExperimentaliTBS 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).
Receives: Device: Repetitive transcranial magnetic stimulation (rTMS)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Chromatic pupillometry

    To extract post-illumination pupil response (PIPR) derived from ipRGCs

    Measured: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)

Secondary outcomes (10)

  1. Optical Coherence Tomography (OCT)

    To extract central retinal thickness and thicknesses of retina neuronal layers (GCL-IPL and RNFL)

    Measured: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)

  2. Pattern Electroretinogram (PERG)

    To extract PERG N95 wave related to RGC function.

    Measured: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)

  3. Contrast sensitivity test

    To measure contrast sensitivity

    Measured: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)

  4. Montgomery-Åsberg Depression Rating Scale (MADRS)

    To evaluate treatment response. Scores range from 0 to 60, with higher scores indicating more severe depressive symptoms.

    Measured: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)

  5. Maudsley Staging Depression

    To assess the level of treatment resistance in depression. Scores range from 3 to 15, with higher scores indicating greater treatment resistance.

    Measured: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)

  6. California Verbal Learning Test-II (CVLT-II)

    To assess verbal learning and memory. Scores range from 0 to 80, with higher scores indicating better verbal learning and memory performance.

    Measured: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)

  7. Reading Mind in Eyes Test (RMET)

    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.

    Measured: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)

  8. Symbol Digit Modalities Test (SDMT)

    To assess information processing speed and attention. Scores range from 0 to 110, with higher scores indicating better cognitive processing speed performance.

    Measured: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)

  9. Brief Visuospatial Memory Test-Revised (BVMT-R)

    To assess visuospatial learning and memory. Scores range from 0 to 36, with higher scores indicating better visuospatial memory performance.

    Measured: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)

  10. WHODAS 12-item (Self-report)

    To assess disability and functional impairment in daily life. Scores range from 12 to 60, with higher scores indicating greater disability.

    Measured: Baseline (pre-intervention), Post-intervention (a day immediately after the end of intervention) and Follow-up (2 months after the end of intervention)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Mar 2026
  2. Study start15 Mar 2026
  3. Primary completion30 Apr 2027 (estimated)
  4. Study completion31 Jul 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07474974
Sponsor's protocol ID
ORT-2026-001
Other IDs
2024.06665.BD, CE0085E
Acronym
BRIGHT
Status last verified
Sep 2026
First submitted
6 Mar 2026
Last updated
13 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Blumberger DM, Vila-Rodriguez F, Thorpe KE, Feffer K, Noda Y, Giacobbe P, Knyahnytska Y, Kennedy SH, Lam RW, Daskalakis ZJ, Downar J. Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Lancet. 2018 Apr 28;391(10131):1683-1692. doi: 10.1016/S0140-6736(18)30295-2. Epub 2018 Apr 26.

    PubMed 29726344

  • Laurenzo SA, Kardon R, Ledolter J, Poolman P, Schumacher AM, Potash JB, Full JM, Rice O, Ketcham A, Starkey C, Fiedorowicz JG. Pupillary response abnormalities in depressive disorders. Psychiatry Res. 2016 Dec 30;246:492-499. doi: 10.1016/j.psychres.2016.10.039. Epub 2016 Oct 21.

    PubMed 27821359

  • Jung KI, Hong SY, Shin DY, Lee NY, Kim TS, Park CK. Attenuated Visual Function in Patients with Major Depressive Disorder. J Clin Med. 2020 Jun 22;9(6):1951. doi: 10.3390/jcm9061951.

    PubMed 32580488

  • Kalenderoglu A, Celik M, Sevgi-Karadag A, Egilmez OB. Optic coherence tomography shows inflammation and degeneration in major depressive disorder patients correlated with disease severity. J Affect Disord. 2016 Nov 1;204:159-65. doi: 10.1016/j.jad.2016.06.039. Epub 2016 Jun 17.

    PubMed 27344626

  • Yildiz M, Alim S, Batmaz S, Demir S, Songur E, Ortak H, Demirci K. Duration of the depressive episode is correlated with ganglion cell inner plexifrom layer and nasal retinal fiber layer thicknesses: Optical coherence tomography findings in major depression. Psychiatry Res Neuroimaging. 2016 May 30;251:60-6. doi: 10.1016/j.pscychresns.2016.04.011. Epub 2016 Apr 18.

    PubMed 27124425

  • De Risio L, Borgi M, Pettorruso M, Miuli A, Ottomana AM, Sociali A, Martinotti G, Nicolo G, Macri S, di Giannantonio M, Zoratto F. Recovering from depression with repetitive transcranial magnetic stimulation (rTMS): a systematic review and meta-analysis of preclinical studies. Transl Psychiatry. 2020 Nov 10;10(1):393. doi: 10.1038/s41398-020-01055-2.

    PubMed 33173042

  • Maruani J, Geoffroy PA. Multi-Level Processes and Retina-Brain Pathways of Photic Regulation of Mood. J Clin Med. 2022 Jan 16;11(2):448. doi: 10.3390/jcm11020448.

    PubMed 35054142

  • Benarroch EE. The melanopsin system: Phototransduction, projections, functions, and clinical implications. Neurology. 2011 Apr 19;76(16):1422-7. doi: 10.1212/WNL.0b013e31821671a5. No abstract available.

    PubMed 21502603

  • Filippatou AG, Calabresi PA, Saidha S, Murphy OC. Spotlight on Trans-Synaptic Degeneration in the Visual Pathway in Multiple Sclerosis. Eye Brain. 2023 Dec 29;15:153-160. doi: 10.2147/EB.S389632. eCollection 2023.

    PubMed 38169913

Questions about this trial

What is this clinical trial studying?

A study testing Repetitive transcranial magnetic stimulation (rTMS) in people with Depression - Major Depressive Disorder and Treatment Resistant Depression, run by Polytechnic Institute of Porto at 1 site in Portugal.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Inês Duarte D Pais, MSc (+351 222 061 000, idp@ess.ipp.pt), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07474974, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2026.

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