Clinical trial NCT05680220: 40 Hz Light Neurostimulation for Patients With Depression (FELIX)
Official title: A Double-blinded, Randomized Placebo-controlled Trial of 40 Hz Light Neurostimulation Therapy for Patients With Depression
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Major Depressive Disorder
Treatment Resistant Depression
Keywords: 40 Hz stimulation
Major Depressive Disorder
Light therapy
GENUS
Lead sponsor: Mental Health Services in the Capital Region, Denmark
Sponsor class: OTHER
Collaborators: name: Technical University of Denmark
name: OptoCeutics
First posted: 2023-01-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Recent research in mice models of Alzheimer's disease (AD) has demonstrated that one hour per day of exposure to 40 Hz flickering light therapy can halt the disease's progression, and improve cognition and memory. Moreover, recent data suggest that 40 Hz light stimulation may induce neuroplasticity and reduce neuroinflammation.

In this study, the investigators aim to evaluate the antidepressant effects of 40 Hz light stimulation in Major Depressive Disorder (MDD). Patients will be exposed to 40 Hz invisible spectral flickering light (active setting) or continuous non-flickering white light (sham setting) in a home setting for 1 hour each day.

Detailed description: Major depression is a major societal challenge worldwide and a substantial proportion of patients do not attain remission. Major depressive disorder (MDD) bears several key neurobiological similarities with Alzheimer's Disease, namely cognitive deficits, impaired neuroplasticity, neurodegeneration, and neuroinflammation. Inducing neuroplasticity and reducing neuroinflammation are thought to be key cellular targets in the treatment of MDD. However, 40 Hz light stimulation research in the context of MDD is limited.

In this double-blinded, randomized placebo-controlled trial the primary objective is to investigate the antidepressant effect of a non-invasive neurostimulation therapy using a 40 Hz masked flickering light. This study utilizes a novel way of masking light by alternating the spectral composition of white light, resulting in the flicker unnoticeable to human perception.

The primary outcome measure of this study is the estimated difference in the Hamilton Depression Rating sub-scale (HAM-D6) scores between groups at week 6. Furthermore, investigators want to assess whether 40 Hz masked flickering light therapy produces a similar early shift in neural and cognitive response to emotional information seen with antidepressant therapy and whether this predicts treatment efficacy. Suicidal ideation, sleep patterns, and quality of life will be also investigated in order to evaluate the 40 Hz masked flickering light stimulation effects on other symptoms of depression. Explorative analysis of the EEG data will be performed from baseline to week 6 for the further development and validation of EEG-based biomarkers.

A total of 60 participants will be enrolled for a six weeks treatment period followed by a two weeks follow-up period. Participants will be recruited from a psychotherapeutic outpatient unit. Medication should be unchanged for the last 4 weeks and during the study period.

Eligibility criteria: Inclusion Criteria:

1. Subjects between 18 and 75 years of age.
2. Subjects with a diagnosis of major depressive episode and currently experiencing a depressive episode according to DSM-5
3. Subjects with an MDI score \&gt; 21 at screening
4. Subjects on stable medication and/or psychotherapy for at least 4 weeks before starting the trial.
5. Subjects, who are willing to comply with the scheduled plan and are able to use the device for 1 hour per day for 6 weeks.
6. Subjects who can understand the oral and written study information and willing to sign an informed consent.

Exclusion Criteria:

1. Subjects with a history of photosensitive migraines and/or epileptic seizures
2. Subjects with a known eye disorder that might be sensitive to light treatment.
3. Subjects with a known history of bipolar disorder according to DSM-5 criteria
4. Subjects with suicidal ideation corresponding to a score of 2 or more on the HAM-D 17 scale item 3 or if the patient or investigator is uncertain of the degree of suicidal risk
5. Subjects with current psychotic symptoms. However, subjects with a prior psychotic depression or subjects with an actual psychotic depression episode that at the time of informed consent no longer fulfills the psychosis criteria are allowed to participate.
6. Subjects with current drug or alcohol dependence based on their medical records or the M.I.N.I. interview.
7. Subjects with a known history of borderline personality disorder
8. Subjects currently enrolled in another investigational treatment study.
9. Subjects with progressive neurodegenerative or neoplastic disease.
10. Subjects who are unable to understand the study procedures or handling of the NSS device.
11. Subjects who are pregnant at the time of inclusion or unsafe contraception in women of fertile age

Primary outcomes:
measure: Depression severity measured by Hamilton Depression Rating sub-scale (HAM-D6)
timeFrame: Baseline and week 6
Secondary outcomes:
measure: Self-reported depression symptoms measured by Major Depression Inventory (MDI)
timeFrame: Baseline, week 1, 3, 6 and 8.
measure: Cognition measured by Facial Expression Recognition Test (FERT)
timeFrame: Baseline, week 1 and 6
measure: Cognition measured by Emotional Categorization and Memory test (ECMT)
timeFrame: Baseline, week 1 and 6
measure: Cognition measured by Screen for Cognitive Impairment in Psychiatry (SCIP)
timeFrame: Baseline, week 1 and 6
measure: Cognition measured by Trail Making Test B (TMT- B)
timeFrame: Baseline, week 1 and 6
measure: Sleep quality measured by Pittsburgh Sleep Quality Index (PSQI)
timeFrame: Baseline, week 3, 6 and 8
measure: Sleep duration
timeFrame: Baseline, week 3, 6 and 8
measure: Sleep timing
timeFrame: Baseline, week 3, 6 and 8
measure: Quality of Life measured by WHO quality of life index (WHO-5)
timeFrame: Baseline, week 3,6 and 8
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Mental Health Centre Copenhagen
Study officials:
affiliation: Senior Consultant at Psychiatric Centre Copenhagen
name: Klaus Martiny
role: PRINCIPAL_INVESTIGATOR
References:
citation: Agger MP, Carstensen MS, Henney MA, Hansen LS, Baandrup AO, Nguyen M, Petersen PM, Madsen KH, Kjaer TW. Novel Invisible Spectral Flicker Induces 40 Hz Neural Entrainment with Similar Spatial Distribution as 40 Hz Stroboscopic Light. J Alzheimers Dis. 2022;88(1):335-344. doi: 10.3233/JAD-220081.
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