40 Hz Visual Stimulation as an Intervention in Schizophrenia

NCT06907420 | Recruiting

• 1 other identifier: RWNM_GammaSZ
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

In schizophrenia, an abnormal reduction in neuronal gamma oscillations (30-100 Hz) is associated with negative symptoms such as cognitive dysfunction. The literature suggests that rescuing gamma oscillations through non-invasive brain stimulation may be an accessible and safe add-on strategy to mitigate negative symptoms. Here, a stimulation protocol based on gamma visual stimulation will be tested. This pilot study will follow an uncontrolled clinical trial design: A minimum of ten patients diagnosed with schizophrenia or a schizoaffective disorder and predominant negative symptoms will be recruited at Klinikum rechts der Isar. They will undergo a multisession stimulation protocol, consisting of one hour of 40 Hz visual stimulation per day over five consecutive days, during which they will be encouraged to fall asleep. An equal number of patients will be recruited for a treatment-as-usual group without intervention. Pre- and post-assessments will include EEG, a cognitive test battery (THINC-IT), a mood scale (PANAS), and a schizophrenia symptom scale (PANSS). This study's results will inform on the feasibility of gamma visual stimulation as a potential add-on intervention in schizophrenia.

Conditions

Negative Symptoms in Schizophrenia; Schizophrenia Disorders; Schizoaffective Disorder

Keywords

gamma; 40 Hz; schizophrenia; visual stimulation; EEG; neuromodulation; flicker; sleep; negative symptoms

Outcome Measures

Primary Outcomes (2)

• Visually evoked neuronal 40 Hz activity represented in the frequency domain

  Steady-State Visually Evoked Potentials (SSVEP) at 40 Hz as an electrophysiological measure of neuronal responses to 40 Hz visual stimulation, represented in the frequency domain. A higher signal-to-noise ratio value at 40 Hz (unit-free), ranging from zero to infinite, represents a larger neuronal response.

  Sessions 1 and 5 (first and last of the five stimulation days)

• Visually evoked neuronal 40 Hz activity represented in the time domain

  Steady-State Visually Evoked Potentials (SSVEP) at 40 Hz as an electrophysiological measure of neuronal responses to 40 Hz visual stimulation, represented in the time domain. A larger peak-to-peak amplitude of the segment average in microvolts, ranging from zero to infinite, represents a larger neuronal response.

  Sessions 1 and 5 (first and last of the five stimulation days)

Secondary Outcomes (4)

• Safety as indicated by the total number and severity of adverse events

  Sessions 1, 2, 3, 4, 5 (from the first throughout the last of the five stimulation days)

• Positive and negative mood assessed by the PANAS scale

  Session 0 (five to one day(s) before the first stimulation) and session 5 (immediately after the last stimulation)

• Schizophrenia negative symptoms measured with the PANSS negative scale

  Five to one day(s) before the first stimulation and zero to three day(s) after the last stimulation

• Cognitive improvement assessed with the THINC-IT test battery

  Session 0 (five to one day(s) before the first stimulation) and session 5 (immediately after the last stimulation)

Study Arms (2)

Visual stimulation

EXPERIMENTAL

1 hour of 40 Hz visual stimulation per day over 5 days in addition to treatment as usual

Device: Visual stimulation

TAU control

NO INTERVENTION

Treatment as usual only

Interventions

Visual stimulation DEVICE

40 Hz visual stimulation will be delivered at the same time of day over 5 consecutive days. Participants will lay down while wearing the customized sleep mask with inbuilt red LEDs flickering at 40 Hz linked to a microcontroller. Participants will be asked to keep their eyes closed and encouraged to fall asleep for the full stimulation duration of 60 minutes.

Visual stimulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Medical diagnosis of schizophrenia (F20) or schizoaffective disorder (F25)

You may not qualify if:

• Age \< 18 years
• Any history of seizures
• Acute suicidality assessed with the Columbia-Suicide Severity Rating Scale (C-SSRS; Brent et al., 2008)
• Any other relevant axis 1 disorder
• Red-green colour blindness or current ocular disease
• Alcohol, cannabis, or illicit drug addiction within the last 3 months

Sponsors & Collaborators

• Technical University of Munich: lead

Study Sites (1)

Technical University of Munich, TUM School of Medicine and Health, Department of Psychiatry and Psychotherapy

Munich, Bavaria, 81675, Germany

RECRUITING

Related Publications (7)

• Vallat R, Walker MP. An open-source, high-performance tool for automated sleep staging. Elife. 2021 Oct 14;10:e70092. doi: 10.7554/eLife.70092.

  PMID: 34648426 BACKGROUND

• Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261-76. doi: 10.1093/schbul/13.2.261.

  PMID: 3616518 BACKGROUND

• Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 1988 Jun;54(6):1063-70. doi: 10.1037//0022-3514.54.6.1063.

  PMID: 3397865 BACKGROUND

• Szmyd JK, Lewczuk K, Teopiz KM, McIntyre RS, Wichniak A. THINC-Integrated Tool (THINC-it): A Brief Measurement of Changes in Cognitive Functioning and Its Correlation with the Life Quality of Patients with Schizophrenia and Related Disorders-A Pilot Study. Brain Sci. 2023 Feb 24;13(3):389. doi: 10.3390/brainsci13030389.

  PMID: 36979199 BACKGROUND

• Harrison JE, Barry H, Baune BT, Best MW, Bowie CR, Cha DS, Culpepper L, Fossati P, Greer TL, Harmer C, Klag E, Lam RW, Lee Y, Mansur RB, Wittchen HU, McIntyre RS. Stability, reliability, and validity of the THINC-it screening tool for cognitive impairment in depression: A psychometric exploration in healthy volunteers. Int J Methods Psychiatr Res. 2018 Sep;27(3):e1736. doi: 10.1002/mpr.1736. Epub 2018 Aug 7.

  PMID: 30088298 BACKGROUND

• Hainke L, Dowsett J, Spitschan M, Priller J. 40 Hz visual stimulation during sleep evokes neuronal gamma activity in NREM and REM stages. Sleep. 2025 Mar 11;48(3):zsae299. doi: 10.1093/sleep/zsae299.

  PMID: 39700417 BACKGROUND

• Brent, D., Lucas, C., Gould, M., Stanley, B., Brown, G., Fisher, P., Zelazny, J., Burke, A., & others. (2008). Columbia-suicide severity rating scale (C-SSRS)

  BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; photopsia

Interventions

Photic Stimulation

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Physical Stimulation; Investigative Techniques

Study Officials

• Ulrike Vogelmann, MD

  TUM School of Medicine and Health, Department of Psychiatry and Psychotherapy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ulrike Vogelmann, MD

CONTACT

+4917661535471; ulrike.vogelmann@mri.tum.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior physician

Study Record Dates

• First Submitted: March 14, 2025
• First Posted: April 2, 2025
• Study Start: March 14, 2025
• Primary Completion: June 1, 2025
• Study Completion: July 1, 2025
• Last Updated: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: IPD and supporting information will be made available immediately after the publication of study results, for an unrestricted duration.
• Access Criteria: The de-identified individual patient data, i.e., all IPD that underlie results in a publication, will be made accessible after its publication for non-commercial academic projects that have a legitimate research topic and a clearly stated hypothesis. In the event that the application is accepted, researchers will be asked to get the study approved by their institution's ethics board. The study principal investigator will subsequently provide the de-identified data sets via a safe data transfer system.

Locations

DE (1)