40 Hz Light Neurostimulation for Patients With Depression (FELIX)

Sponsor

Klaus Martiny (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05680220

Collaborator

Technical University of Denmark (Other), OptoCeutics (Industry)

Enrollment

Location

Arms

Anticipated Duration (Months)

3.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder Treatment Resistant Depression	Device: Neurostimulation System (NSS): Active Setting Device: Neurostimulation System (NSS): Sham Setting	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Double-blinded, Randomized Placebo-controlled Trial of 40 Hz Light Neurostimulation Therapy for Patients With Depression

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Neurostimulation System (NSS) Exposure to the NSS device set to 40 Hz invisible spectral flicker 1 hour a day	Device: Neurostimulation System (NSS): Active Setting Exposure to the active device for 1 hour a day for 6 weeks
Placebo Comparator: Sham Neurostimulation System (NSS) Exposure to the NSS device set to continuous color-matched white light for 1 hour a day	Device: Neurostimulation System (NSS): Sham Setting Exposure to the sham device for 1 hour a day for 6 weeks

Arm

Intervention/Treatment

Experimental: Active Neurostimulation System (NSS)

Exposure to the NSS device set to 40 Hz invisible spectral flicker 1 hour a day

Device: Neurostimulation System (NSS): Active Setting

Exposure to the active device for 1 hour a day for 6 weeks

Placebo Comparator: Sham Neurostimulation System (NSS)

Exposure to the NSS device set to continuous color-matched white light for 1 hour a day

Device: Neurostimulation System (NSS): Sham Setting

Exposure to the sham device for 1 hour a day for 6 weeks

Outcome Measures

Primary Outcome Measures

Depression severity measured by Hamilton Depression Rating sub-scale (HAM-D6) [Baseline and week 6]
The HAM-D6 scale is designed to rate the severity of depression by a healthcare professional. The assessment scale contains 6 items pertaining to the symptoms of depression experienced over the week. The primary endpoint is the mean difference in scores between treatments at baseline and week 6. The score range is from, 0-24 (24=highest depression level).

Secondary Outcome Measures

Self-reported depression symptoms measured by Major Depression Inventory (MDI) [Baseline, week 1, 3, 6 and 8.]
The MDI is a depression self-assessment questionnaire. It consists of the 10 ICD-10 symptoms for depression. The sum of 10 questions indicates the degree of depression. The score range is from 0-50 (50=highest depression level).
Cognition measured by Facial Expression Recognition Test (FERT) [Baseline, week 1 and 6]
Assessing attention and recognition of emotional facial expressions using the FERT. The outcome is accuracy (% correct expressions identified, range: 0-100, higher is better) and response times for accurate identifications (milliseconds, range can vary quite a bit, smaller number is better because it reflect higher speed).
Cognition measured by Emotional Categorization and Memory test (ECMT) [Baseline, week 1 and 6]
Assessing self-referent memory for emotional words using the ECMT. Outcome is response times for correct identifications during encoding phase (milliseconds, smaller better) and for recall phase: number of positive and negative words recalled (higher is better)
Cognition measured by Screen for Cognitive Impairment in Psychiatry (SCIP) [Baseline, week 1 and 6]
Non-emotional cognition is investigated with the SCIP. Outcomes is total score as well as scores for the five subtests, in all cases higher is better (numbers correct)
Cognition measured by Trail Making Test B (TMT- B) [Baseline, week 1 and 6]
Non-emotional cognition investigated with the Trail Making Test B (TMT- B). Outcome is time in seconds to complete the task, lower is better (higher speed)
Sleep quality measured by Pittsburgh Sleep Quality Index (PSQI) [Baseline, week 3, 6 and 8]
PSQI consist of seven component scores that are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality. A cut-off of 5 is recognized a indicative of sleep problems.
Sleep duration [Baseline, week 3, 6 and 8]
Average sleep duration assessed over last 7 days will be logged by the participants using a sleep diary.
Sleep timing [Baseline, week 3, 6 and 8]
Average sleep timing will be assessed over last 7 days logged by the participants using a sleep diary.
Quality of Life measured by WHO quality of life index (WHO-5) [Baseline, week 3,6 and 8]
The WHO-5 score ranges from 0 to 25, with 0 representing worst possible and 25 representing best possible quality of life. To obtain a percentage score ranging from 0 to 100, the raw score is multiplied by 4. A percentage score of 0 represents worst possible, whereas a score of 100 represents best possible quality of life. A 10% difference indicates a significant change.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects between 18 and 75 years of age.
Subjects with a diagnosis of major depressive episode and currently experiencing a depressive episode according to DSM-5
Subjects with an MDI score > 21 at screening
Subjects on stable medication and/or psychotherapy for at least 4 weeks before starting the trial.
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.
Subjects who can understand the oral and written study information and willing to sign an informed consent.

Exclusion Criteria:

Subjects with a history of photosensitive migraines and/or epileptic seizures
Subjects with a known eye disorder that might be sensitive to light treatment.
Subjects with a known history of bipolar disorder according to DSM-5 criteria
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
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.
Subjects with current drug or alcohol dependence based on their medical records or the M.I.N.I. interview.
Subjects with a known history of borderline personality disorder
Subjects currently enrolled in another investigational treatment study.
Subjects with progressive neurodegenerative or neoplastic disease.
Subjects who are unable to understand the study procedures or handling of the NSS device.
Subjects who are pregnant at the time of inclusion or unsafe contraception in women of fertile age