IWLS for Major Depressive Disorder: An Open-Label Study of Safety, Tolerability, and Efficacy (IWLS-MDD)

Intermittent White Light Stimulation (IWLS) for the Treatment of Major Depressive Disorder: An Open-Label Pilot Study of Safety, Tolerability, and Preliminary Efficacy

INTRODUCTION:

Depression is the most common mood disorder worldwide, with approximately 20 million adults affected in the United States in 2019. Current pharmacological treatments are not effective for all patients, often have significant side effects, and in some cases, require medical monitoring. Non-invasive brain stimulation (NIBS) techniques are emerging as a promising therapeutic alternative, offering fewer side effects. In this context, 60 Hz intermittent light stimulation may represent a promising and safe treatment option for depression. Animal studies have demonstrated that this form of stimulation can promote neuroplasticity, while studies in healthy individuals have shown the technique to be safe. However, 60 Hz intermittent light stimulation has not yet been evaluated in depressed patients in clinical trials.

METHODS:

This is an open-label study designed to assess the safety and tolerability of 60 Hz intermittent light stimulation (ILS) in individuals with moderate to severe depression. The trial will last six weeks in total, consisting of five sessions per week during the first two weeks, with one daily session (a total of 10 sessions, each lasting 30 minutes with 60 Hz white light stimulation), followed by two follow-up visits at weeks 4 and 6. Thirty patients aged 18 to 59 years will be recruited, with a current diagnosis of a mild major depressive episode (HDRS-17 scores between 8 and 23) and on a stable antidepressant regimen for at least six weeks.The primary outcome will be the safety and tolerability of the device. Clinical improvement will be assessed through changes in HDRS-17 scores and other validated depression and anxiety scales.

EXPECTED RESULTS:

The results of this pilot study may advance knowledge in the field and pave the way for future placebo-controlled clinical trials.

Study Overview

• Status: Active, not recruiting
• Conditions: Major Depressive Disorder (MDD)
• Intervention / Treatment: Device: Intermittent White Light Stimulation (IWLS)

Detailed Description

This is an open-label pilot study evaluating the safety, tolerability, and preliminary efficacy of Intermittent White Light Stimulation (IWLS) in individuals with moderate to severe Major Depressive Disorder. The intervention consists of 10 sessions over two weeks, with follow-up at weeks 4 and 6. The study aims to gather data to support future randomized controlled trials using IWLS for depression.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • São Paulo, São Paulo, Brazil, 05403-010
      • University of Sao Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age between 18 and 65 years;
• Current diagnosis of Major Depressive Disorder (MDD), confirmed by MINI; HDRS-17 score between 8 and 23 at baseline;
• Stable antidepressant regimen for at least 6 weeks prior to enrollment;
• Able and willing to provide informed consent.

Exclusion Criteria:

• Diagnosis of other psychiatric disorders (e.g., bipolar disorder, psychotic disorders, OCD, ADHD, personality disorders, dementia);
• Substance or alcohol use disorders;
• Severe suicidal ideation or psychotic symptoms;
• HDRS-17 score >28;
• Neurological or severe medical conditions;
• History of epilepsy, migraine, or photosensitivity;
• Retinal disease or cataracts;
• Regular use of anti-inflammatory medications or clopidogrel;
• Any worsening of symptoms during the trial (e.g., psychosis, HDRS >28, or suicidal ideation);
• Participation in another clinical trial within the last 30 days.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: IWLS Intervention; Participants in this arm will receive Intermittent White Light Stimulation (IWLS) at 60 Hz using an LED-equipped eye mask. Sessions will occur once daily (Monday to Friday) for 2 consecutive weeks, totaling 10 sessions. Each session will last 30 minutes. Follow-up assessments will be conducted at weeks 4 and 6 after the intervention period. The device used is developed by SyntropicMedical (Austria) and emits approximately 700 lux of diffuse white light delivered tangentially to the eyes.

Device: Intermittent White Light Stimulation (IWLS); A wearable device developed by SyntropicMedical (Austria) delivers intermittent white light at 60 Hz using LED strips embedded in safety goggles. The light is diffused (approximately 700 lux) and projected tangentially to the participant's eyes. Participants will undergo 10 daily sessions (30 minutes each) over a two-week period. The intervention aims to evaluate the safety, tolerability, and potential antidepressant effects of 60 Hz visual stimulation in individuals with moderate to severe Major Depressive Disorder.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability of Intermittent White Light Stimulation (IWLS)	Safety and tolerability will be assessed through adverse events reported by participants during the stimulation period and follow-up, as well as dropout rates. Adverse effects such as dry eyes, headache, drowsiness, or discomfort will be recorded using a structured questionnaire. Ophthalmologic examinations will be conducted at baseline and at 6 weeks.	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Depression Severity as Measured by HDRS-17	Depressive symptoms will be evaluated using the 17-item Hamilton Depression Rating Scale (HDRS-17). Outcomes will include change from baseline, clinical response (≥50% reduction), and remission (score <7) at Days 12 and 40.	Baseline, Day 12, Day 40

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Investigators: Study Director: Kallene Vidal, Doctor, University of Sao Paulo

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2025
• Primary Completion (Actual): November 1, 2025
• Study Completion (Estimated): May 30, 2026

Study Registration Dates

• First Submitted: April 3, 2025
• First Submitted That Met QC Criteria: April 3, 2025
• First Posted (Actual): April 11, 2025

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: light; major depression; open-label clinical trial; 60 Hz
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 84990324.7.0000.0068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: De-identified individual participant data (IPD) that underlie the results reported in this study will be shared, including data on primary and secondary outcomes, adverse events, and baseline characteristics.
• IPD Sharing Time Frame: Study protocol, statistical analysis plan (SAP), informed consent form (ICF), and clinical study report (CSR) will be made available upon request.
• IPD Sharing Access Criteria: Data will be available starting 6 months after publication of the primary results and will be available for a period of 5 years.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

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