Light Therapy in Parkinson's Disease

Study Overview
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Brief Summary
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The aim of this randomized controlled trial (RCT) is to clarify the effect of bright light therapy on motor symptoms and sleep disorders in patients with Parkinson's disease.

Detailed Description
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As the most important biologic rhythm timer, exogenous light supplement has certain benefits for the improvement of sleep quality and dementia. At present, it is gradually used in sleep and neuropsychiatric diseases. In an open study, 120 patients with PD received 4000 to 6000 lux of light, for 60 minutes before habitual bedtime. The patients were followed up for several months to 8 years, and it found the patients who persisted in the treatment improved their mood, anxiety and motor function. Clinical studies have confirmed the safety and effectiveness of light in improving insomnia and daytime sleepiness of PD patients. It was found that strong light can significantly improve the patients' motor and non-motor symptoms. However, these findings have not been reported in Chinese PD patients. The aim of this randomized controlled trial (RCT) is to clarify the effect of bright light therapy on motor symptoms and sleep disorders in patients with Parkinson's disease and explore the possible mechanism.

Official Title
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Light Therapy in Parkinson's Disease: a Prospective, Observational Study

Conditions
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Parkinson Disease, Sleep Disorder, Circadian Rhythm Disorders

Intervention / Treatment
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* Device: Bright light box
* Device: Dim Light box


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: According to the criteria of PD diagnosis of the MDS, PD patients were selected as the research object. The clinical symptoms of PD patients were consistent with Hoehn and Yahr stages 2-3. All PD patients have maintained stable drug treatment for at least one month, signed clinical informed consent and agreed not to adjust drugs throughout the light test and follow-up period. Exclusion Criteria: Using hypnotic or stimulating drugs. Using antidepressants, except stable drugs maintained for more than three months; Visual impairment, such as cataract, glaucoma, blindness, etc; Cognitive impairment (MMSE < 24); There are uncontrollable hallucinations and mental diseases; There are sleep phase delay / advance syndrome, shift work, jet lag, etc

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Dim light group<br>treated with the placebo device which operates with one intensity of 300 lux * 1 month | Device: Dim Light box<br>* The light box uses a spectrally transparent prism diffuser, which can block ultraviolet rays, but will not affect the quality of the filtered light and will not turn yellow. The distance between the light box and the patient should not exceed 65cm.PD patients are selected for light intervention of different intensities. The control group is treated with 300 Lux intensity. The treatment time is 1 hour each day from 09:00-11:00 in the morning and 17:00-19:00 in the afternoon lasting for a month. The patient is asked to move under the light source, but should not fall asleep.<br>|
| Experimental: Bright light group<br>treated with the experimental device which operates with one intensity of 10,000 lux * 1 month | Device: Bright light box<br>* The light box uses a spectrally transparent prism diffuser, which can block ultraviolet rays, but will not affect the quality of the filtered light and will not turn yellow. The distance between the light box and the patient should not exceed 65cm.PD patients are selected for light intervention of different intensities. The experimental group is treated with 10,000 Lux intensity. The treatment time is 1 hour each day from 09:00-11:00 in the morning and 17:00-19:00 in the afternoon lasting for a month. The patient is asked to move under the light source, but should not fall asleep.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in total sleep time(TST) by polysomnography (PSG) at 12 weeks | Total sleep time is the sum of sleep time in each period. This outcome reflects change of patients' sleep quality. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Changes from baseline in sleep efficient by polysomnography (PSG) at 12 weeks | Sleep efficiency is the ratio of the total time spent asleep (total sleep time) in a night compared to the total amount of time spent in bed. This outcome reflects change of patients' sleep quality. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Change from baseline in REM sleep without atonia by (RWA) polysomnography (PSG) at 12 weeks | REM sleep without atonia (RWA) is the PSG finding of persistent muscle tone during REM sleep, resulting in paroxysmal phasic or tonic EMG activity. Together with dream-enacting behavior (DEB), RSWA is a necessary diagnostic criterion of REM sleep behavior disorder (RBD). This outcome reflects change of RBD severity. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Change from baseline in sleep onset latency polysomnography (PSG) at 12 weeks | Sleep latency is the amount of time it takes patients to go from being fully awake to sleeping. Patients' sleep latency and how quickly they reach rapid eye movement (REM) sleep can be indicators of the amount and quality of sleep they are getting. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Change from baseline in Periodic Limb Movement during Sleep(PLMS) by polysomnography (PSG) at 12 weeks | Periodic limb movement during sleep (PLMS) is is described as a stereotypical involuntary movement during sleep. In particular, presenting more than 15 periodic limb movements per hour is related to daytime sleepiness due to low sleep quality. This outcome reflects change of patients' sleep quality. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in Unified Parkinson's Disease Rating Scale (UPDRS) score at 12 weeks | Unified Parkinson's Disease Rating Scale (UPDRS) is an effective tool to evaluate the severity of motor symptoms in patients with Parkinson's disease (PD).Each item is simply given a 5- point score: 0 (Absent) to 4 (Marked in amplitude and present most of the time).The higher the UPDRS score is, the worse the symptoms are. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Changes form baseline in Hoehn-Yahr scale at 12 weeks | In H-Y scale, PD is divided into 5 stages according to the range and extent of motor symptoms. The higher the H-Y scale is, the worse the symptoms are. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Changes form baseline in PDSS score scale at 12 weeks | The Parkinson's Disease Sleep Scale(PDSS) assesses a wide spectrum of disease-specific sleep problems. The best cut-off score was 120.The higher the PDSS is, the better the sleep quality is. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Changes form baseline in Pittsburgh sleep quality index (PSQI) score at 12 weeks | The Pittsburgh sleep quality index (PSQI) is widely used to measure sleep quality. The best cut-off score was 7. The higher the PSQI score is, the worse the sleep quality is. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Changes from baseline in REM sleep behavior disorder questionnaire-Hong Kong (RBDQ-HK) score at 12 weeks | REM sleep behavior disorder questionnaire-Hong Kong (RBDQ-HK) is widely used to assess the severity of RBD. The higher RBD-HK score is, the worse the symptoms are. In East China, the best cut-off value for RBDQ-HK was located at 17 with a sensitivity of 85% and specificity of 81% (AUC = 0.892) . | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Changes from baseline in Epworth sleepiness scale (ESS) score at 12 weeks | The Epworth sleepiness scale (ESS) measures daytime sleepiness. The best cut-off score was 10.The higher the ESS score is, the worse the fatigue symptoms are. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Changes from baseline in Morningness-Eveningness Questionnaire (MEQ) score at 12 weeks | The Morningness-Eveningness Questionnaire (MEQ) is the most widely known questionnaire to assess circadian preference. Cut-off points were evaluated: a range of 14-52 for Evening types, 53-64 for neither types, and 65-86 for Morning types. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Changes from baseline in Hamilton Anxiety Scale(HAMA) score at 12 weeks | The Hamilton Anxiety Scale(HAMA) is a widely used interview scale to measure the severity of a patient's anxiety . The HAMA score can range from 0 to 56. The higher the HAMA score is, the worse the symptoms are. The best cut-off score was14. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Changes from baseline in Hamilton Depression Scale-24(HAMD-24) score at 12 weeks | The Hamilton Depression Scale-24(HAMD-24) is a test measuring the severity of depressive symptoms in individuals. The HAMA score can range from 0 to 56. The higher the HAMA score is, the worse the symptoms are.An optimal HAMD-24 cut-off score for distinguishing between patients with and without a depressive disorders was found to be 9/10,with a high area under the curve(AUC) (0.91) indicating excellent discrimination. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Changes in Montreal Cognitive Assessment (MoCA) score at 12 weeks | Montreal Cognitive Assessment (MoCA) is widely used to assess cognitive dysfunction. The MoCA score can range from 0 to 30.The best cut-off score was 26. The higher the HAMA score is, the better the cognitive function is. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Changes from baseline in Non-Motor Symptoms Questionnaire at 12 weeks | Non-Motor Symptoms Questionnaire(NMSQ)contains 30 items and requires patients to answer yes and no according to their own situation in the last month. It is widely used in the assessment of PD patients' non motor symptoms. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Changes from baseline in Parkinson's Disease Questionnaire (PDQ-39) at 12 weeks | The Parkinson's Disease Questionnaire (PDQ-39) is the most frequently used disease-specific health status measure.PDQ-39 total score equal or above 47 was the optimal cut-off associated with a high caregiver strain with a sensitivity of 83% and a specificity of 64% . | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Changes from baseline in Fatigue Severity Scale (FSS) at 12 weeks | The Fatigue Severity Scale (FSS) is a scale used in the evaluation of fatigue that affects patients. A list of 9 statements is provided. The best cut-off score was 4. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Changes from baseline in electroencephalogram(EEG) at 12 weeks | Amplitudes of various frequency bands in each cortical region of EEG reflects change of cortical activity. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Changes from baseline in the rhythmic level of melatonin in serum and saliva at 12 weeks | We collected saliva of participants in sections for 24 hours (6:00, 9:00, 12:00, 15:00, 18:00, 19:00, 20:00, 21:00, 22:00, 23:00, ten time points in total) and serum（8：00，20：00）to detect the level of melatonin. This outcome reflects change of biological rhythm. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) | 
| Changes from baseline in the rhythmic level of cortisol in serum and saliva at 12 weeks | We collected saliva of participants in sections for 24 hours (6:00, 9:00, 12:00, 15:00, 18:00, 19:00, 20:00, 21:00, 22:00, 23:00, ten time points in total) and serum（8：00，20：00）to detect the level of cortisol. This outcome reflects change of biological rhythm. | visit1(baseline),visit2(4th week),visit3(8th week),visit4(12th week) |