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RecruitingNCT07474974BRIGHTUpdated Oct 13, 2026

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

An interventional study of Repetitive transcranial magnetic stimulation (rTMS) in Depression - Major Depressive Disorder and Treatment Resistant Depression, sponsored by Polytechnic Institute of Porto. Recruiting at 1 site in Portugal. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-10-13.

Sponsored by Polytechnic Institute of Porto · Not applicable, Interventional, and Treatment

From the registry’s dates

  • Started Mar 2026; still recruiting 7 months later.
Updated Oct 13, 2026Study contact changedGo to Updates ↓
Phase
Not applicable
Study type
Interventional
Enrollment
44
Allocation
Not applicable
Ages
18 Years to 65 Years
Sex
All
01

Study 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). 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.

02

Conditions studied

  • Depression - Major Depressive Disorder
  • Treatment Resistant Depression

Keywords

  • Major Depressive Disorder
  • Repetitive Transcranial Magnetic Stimulation
  • Retinal Ganglion Cells
  • ipRGCs
  • Treatment-resistant depression
03

In context

Depressive Disorder, Treatment-Resistant

448 studies on the registry are indexed under Depressive Disorder, Treatment-Resistant; 147 are open to participants now.

This study's planned enrollment of 44 is below the median of 59 across 372 interventional studies indexed under Depressive Disorder, Treatment-Resistant.

Browse Depressive Disorder, Treatment-Resistant studies →

Lead sponsor

Polytechnic Institute of Porto is the lead sponsor of 14 studies on the registry; 6 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

Exclusion Criteria:

  • Prior rTMS treatment;
  • 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.
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
44 participants (estimated)

Study arms

  • 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)

Interventions

  • DeviceRepetitive 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.

    Also known as: Active rTMS, DLPFC rTMS, Active iTBS, iTBS

06

What researchers measure

Primary outcomes

  1. Chromatic pupillometry

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

    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)

Secondary outcomes

  1. Optical Coherence Tomography (OCT)

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

    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)

  2. Pattern Electroretinogram (PERG)

    To extract PERG N95 wave related to RGC function.

    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)

  3. Contrast sensitivity test

    To measure contrast sensitivity

    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)

  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.

    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)

  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.

    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)

  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.

    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)

  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.

    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)

  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.

    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)

  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.

    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)

  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.

    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)

07

Study locations

1 of 1 sites recruiting
  • RISE-Health, Center for Translational Health and Medical Biotechnology Research (TBIO), School of Health, Polytechnic of Porto
    Porto, Porto District 4200-072, Portugal
    Recruiting
08

References and documents

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 ↗

Individual participant data

Plan to share: No

09

Timeline

1 registry update since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Started Mar 2026 (actual). Primary completion is estimated for Apr 2027, 13 months after the start.

Of 135 non-industry interventional studies with no phase under Depressive Disorder, Treatment-Resistant, half reached primary completion within 42 months of starting (the median), counting those still running; a quarter within 22 and three quarters within 79. This study's planned 13 months is below that.

Counting every sponsor, half of 139 studies reached it within 50 months; a quarter within 22 and three quarters within 88.

How these figures are worked out, and which studies are left out of them.

Registered
Mar 6, 2026
First posted
Mar 16, 2026
StartActual
Mar 15, 2026
Primary completionEst.
Apr 30, 2027
CompletionEst.
Jul 31, 2027
Last update
Oct 13, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Contact
Study contact's phone or email changed: •••0656→•••1000; •••4780→•••1000. See the current contact
Oct 13, 2026
Show all 1 update
  1. Oct 13, 2026
    Contact Study contact's phone or email changed: •••0656→•••1000; •••4780→•••1000. See the current contact

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT07474974
Lead sponsor
Polytechnic Institute of Porto
Collaborators
Hospital de Sao Joao, Porto
Responsible party
Catarina Mateus, PhD (Associate Professor, Polytechnic Institute of Porto) — Principal investigator
First posted
Mar 16, 2026
Start date
Mar 15, 2026
Primary completion
Apr 30, 2027 (estimated)
Completion
Jul 31, 2027 (estimated)
Last update
Oct 13, 2026

Study contacts

Inês Duarte D Pais, MSc
Contact
idp@ess.ipp.pt
+351 222 061 000
Catarina C Mateus, PhD
Contact
cms@ess.ipp.pt
+351 222 061 000
Catarina C Mateus, PhD
study director · Polytechnic Institute of Porto

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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