NCT07474974

Brief 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.

Trial Health

65
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
44

participants targeted

Target at P25-P50 for not_applicable

Timeline
12mo left

Started Mar 2026

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress28%
Mar 2026Jul 2027

First Submitted

Initial submission to the registry

March 6, 2026

Completed
9 days until next milestone

Study Start

First participant enrolled

March 15, 2026

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 16, 2026

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 30, 2027

Expected
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2027

Last Updated

March 16, 2026

Status Verified

March 1, 2026

Enrollment Period

1.1 years

First QC Date

March 6, 2026

Last Update Submit

March 11, 2026

Conditions

Depression - Major Depressive DisorderTreatment Resistant Depression

Keywords

Major Depressive DisorderRepetitive Transcranial Magnetic StimulationRetinal Ganglion CellsipRGCsTreatment-resistant depression

Outcome Measures

Primary Outcomes (1)

  • Chromatic pupillometry

    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 Outcomes (10)

  • Optical Coherence Tomography (OCT)

    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)

    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

    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)

    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

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

  • +5 more secondary outcomes

Study Arms (1)

iTBS

EXPERIMENTAL

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

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.

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

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (9)

  • 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.

    PMID: 29726344BACKGROUND

  • 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.

    PMID: 27821359BACKGROUND

  • 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.

    PMID: 32580488BACKGROUND

  • 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.

    PMID: 27344626BACKGROUND

  • 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.

    PMID: 27124425BACKGROUND

  • 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.

    PMID: 33173042BACKGROUND

  • 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.

    PMID: 35054142BACKGROUND

  • 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.

    PMID: 21502603BACKGROUND

  • 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.

    PMID: 38169913BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Treatment-ResistantDepressive Disorder, Major

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field TherapyTherapeutics

Study Officials

  • Catarina C Mateus, PhD

    Polytechnic Institute of Porto

    STUDY DIRECTOR

Central Study Contacts

Inês Duarte D Pais, MSc

CONTACT

+351 917750656idp@ess.ipp.pt

Catarina C Mateus, PhD

CONTACT

+351 962662157cms@ess.ipp.pt

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

March 6, 2026

First Posted

March 16, 2026

Study Start

March 15, 2026

Primary Completion (Estimated)

April 30, 2027

Study Completion (Estimated)

July 31, 2027

Last Updated

March 16, 2026

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will not share