40 Hz Flickering for Insomnia in Parkinson's Disease

Official title

Randomized, Single-blind, Controlled Study of 40 Hz Flickering Stimulation for Insomnia and Other Non-motor Symptoms in Patients With Parkinson's Disease

Overview

This randomized, single-blind, controlled clinical trial aims to evaluate the efficacy and safety of 40 Hz flicker light stimulation for insomnia in patients with Parkinson's disease (PD). Patients with PD and clinically significant insomnia will be randomly assigned in a 1:1 ratio to receive either 40 Hz flicker light or control light for 30 minutes every night at bedtime for 7 consecutive days, in addition to standard antiparkinsonian treatment. The primary objective is to determine whether 40 Hz flicker light stimulation improves PD-related insomnia as measured by Parkinson's Disease Sleep Scale-2 (PDSS-2). Secondary objectives include evaluating changes in polysomnography-derived sleep parameters, subjective sleep quality, and other non-motor symptoms, as well as assessing the safety and tolerability of the intervention. This registration specifically covers the Parkinson's disease insomnia cohort of a larger, previously approved multi-cohort protocol that also includes healthy volunteers and primary insomnia patients.

Detailed description

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by both motor and non-motor symptoms. Insomnia and other sleep disturbances are highly prevalent in PD and significantly impair quality of life, yet current pharmacological therapies are often insufficient and may produce adverse effects. There is a clear need for novel, non-pharmacological approaches to improve sleep in PD.

Gamma-band (around 40 Hz) neural oscillations are associated with cortical network activity and may influence sleep regulation, brain adenosine levels, and glymphatic clearance. Flicker light stimulation at 40 Hz has been shown in preclinical and early clinical studies to modulate gamma oscillations and related neurophysiological processes. Based on these findings, 40 Hz visual flicker stimulation may represent a promising, non-invasive strategy for improving insomnia and other non-motor symptoms in PD.

In this single-center, randomized, single-blind, controlled trial, approximately 30 patients with PD and clinically significant insomnia will be enrolled. Eligible participants will be randomly assigned to receive either 40 Hz flicker light stimulation or control light. Participants in the 40 Hz group will receive visual flicker stimulation at 40 Hz for 30 minutes every night at bedtime for 7 consecutive days, using a dedicated light device, in addition to their stable antiparkinsonian medication. Participants in the control group will receive non-40 Hz light of similar intensity and duration under otherwise identical conditions.

Clinical assessments will include PD-specific sleep scales, particularly the Parkinson's Disease Sleep Scale-2 (PDSS-2), general sleep questionnaires such as the Pittsburgh Sleep Quality Index (PSQI), and sleep diaries. Objective sleep parameters, including total sleep time, sleep efficiency, sleep latency, wake after sleep onset, and number of nocturnal awakenings, will be obtained from polysomnography where applicable. Other non-motor symptoms may also be evaluated using standardized scales. Safety assessments will include monitoring of adverse events, vital signs, and visual or ophthalmic discomfort during and after stimulation.

The parent protocol, initially approved in 2022, included healthy volunteers and primary insomnia patients. The present registration focuses exclusively on the Parkinson's disease insomnia cohort introduced by later protocol amendments and does not include the non-PD cohorts.

Interventions

• Device 40 Hz flicker light device
  A visual stimulation device delivering flicker light at 40 Hz. Participants assigned to this intervention receive 30 minutes of 40 Hz flicker light stimulation every night at bedtime for 7 consecutive days, in addition to their stable antiparkinsonian medication. Device parameters, including light intensity and distance, are adjusted according to the protocol to ensure safety and comfort.
• Device 100 Hz flicker light device
  A visual stimulation device delivering 100 Hz light (e.g., steady or low-frequency light) with similar appearance and intensity as the 40 Hz device. Participants assigned to this intervention receive 30 minutes of control light exposure every night at bedtime for 7 consecutive days, in addition to their stable antiparkinsonian medication.

Primary outcome measures

• Change in Parkinson's Disease Sleep Scale-2 (PDSS-2) total score (0-60 points; higher scores indicate worse sleep disturbance). [Time frame: Baseline and Day 7]

Secondary outcome measures (2)

• Change in Parkinson's Disease Sleep Scale-2 (PDSS-2) total score at follow-up (0-60 points; higher scores indicate worse sleep disturbance). [Time frame: Baseline, Day 7, and Day 28]
• Change in Non-Motor Symptoms Scale (NMSS) total score (0-360 points; higher scores indicate more severe non-motor symptoms). [Time frame: Baseline and Day 7]

Eligibility criteria

Inclusion criteria

• Diagnosis of Parkinson's disease according to established clinical criteria (e.g., Movement Disorder Society criteria).
• Age between 50 and 75 years.
• Disease duration ≤ 10 years and Hoehn and Yahr stage ≤ 3 in the "on" state.
• Clinically significant insomnia, defined as Parkinson's Disease Sleep Scale-2 (PDSS-2) total score ≥ 18 points and/or meeting diagnostic criteria for insomnia.
• Stable antiparkinsonian medication regimen for at least 4 weeks prior to enrollment.
• Able and willing to comply with study procedures and provide written informed consent.

Exclusion criteria

• Secondary insomnia primarily due to severe systemic diseases or major psychiatric disorders (e.g., psychosis, severe depression or anxiety) or substance abuse.
• History of epilepsy, photosensitive seizures, photosensitive dermatitis, or other conditions in which flicker light stimulation is contraindicated.
• Severe visual impairment or eye diseases that would interfere with light stimulation or safety assessment.
• Unstable or severe medical conditions (e.g., uncontrolled cardiovascular, hepatic, renal, or endocrine disease) that, in the investigator's opinion, make participation unsafe.
• Participation in another interventional clinical trial within the past 3 months.
• Inability to complete study procedures or follow-up due to cognitive, physical, or social reasons.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• The Affiliated Brain Hospital of Nanjing Medical University, 264 Guangzhou Road — Nanjing

Identifiers

NCT: NCT07323121 · 2022-130-K-99-01 · 82430045

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗