Non-visual Photoreception
Conditions
Keywords
Melatonin, Sleep, Light, Alertness, Circadian Rhythms
Brief summary
The timing and quality of sleep is governed by environmental and physiologic factors. Environmental factors, especially ambient lighting can impact the circadian system and alter the timing and structure of sleep. Light exposure can also acutely alter neural activation state and impair sleep. These effects all demonstrate marked sensitivity to short-wavelength blue light with maximal sensitivity in the 460-480 nm range. The alerting effects of blue light in the evening persist for at least 3-4 hours after the lights are turned off, and can disturb subsequent sleep. Avoiding these deleterious effects of light exposure prior to sleep on subsequent sleep would be beneficial to sleep quality and potentially health. The investigators will compare the effects of two light sources, equated for visual stimulus (lux), on multiple non-visual responses to light. The investigators will compare a 90 lux exposure of a commercially available Compact Fluorescent Light (CFL) with a novel LED white light source that is depleted in the short-wavelength visible range (Biological Illumination LCC, FL). In a within-subject design, the investigators will test the hypotheses that exposure to a blue-depleted LED as compared to a CFL exposure at (1) 90 lux or (2) 50 lux will cause significantly: 1. Less melatonin suppression between melatonin onset and bedtime; 2. Less subjective and objective alerting responses before bedtime; 3. Less disruption of nocturnal sleep structure and quality.
Interventions
DEVICEVisible light
We will compare the effects of two light sources, equated for visual stimulus (lux), on multiple non-visual responses to light including melatonin suppression before bedtime. We will compare a 90 lux exposure of a commercially available Compact Fluorescent Light (CFL) with a novel LED white light source that is depleted in the short-wavelength visible range (Biological Illumination LCC, FL).
Sponsors
Biological Illumination, LLC
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Intervention model description
Stratified randomized crossover trial. Participants randomized between CFL and LED conditions stratified by light intensity (50 lux and 90 lux).
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
(i) Aged between 18-30 years to reduce the confounding effects of lens aging on the transmission of light to the retina; (ii) Non-smoking for at least 6 months; (iii) Healthy (no medical, psychiatric or sleep disorders); (iv) No clinically significant deviations from normal in medical history, vital signs, physical examination, blood chemistry and hematology, urine chemistry and ECG; (v) Women of childbearing potential must agree to use an acceptable method of birth control, and must have a negative urine pregnancy test; (vi) Body mass index of \> 18 or \< 30 kg/m2; (vii) No drugs or medication likely to affect sleep or alertness, as determined by the investigators; (viii) Habitual caffeine consumption \< 300mg per day on average; (ix) Habitual alcohol consumption \< 10 alcoholic units per week on average.
Exclusion criteria
(i) History of alcohol or substance abuse; (ii) Positive result on drugs of abuse screening; (iii) Current or past history of sleep disorders, including but not limited to obstructive sleep apnea, or any significant sleep complaint; (iv) Psychiatric disorder; (v) Recent acute or chronic medical disorder, including but not limited to hepatic impairment and severe chronic obstructive pulmonary disease; (vi) Visual disorder, including but not limited to color blindness, or family history of glaucoma; (vii) History of intolerance or hypersensitivity to melatonin or melatonin agonists; (viii) Pregnancy or lactation; (ix) Shift work; (x) Transmeridian travel (2 or more time zones) in past 2 months; (xi) Any other reason as determined by the Principal Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Melatonin Suppression | 6-h constant posture interval of the light exposure | Melatonin suppression is measured as the percentage of melatonin AUC relative to the AUC measured in dim light on the previous day. AUC was calculated during the 6 h of light exposure and the corresponding 6-h interval 24 hours earlier. Higher values indicate more light-induced melatonin suppression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Structure | 8-h time in bed immediately following CFL/LED light exposure. | Sleep efficiency assessed by polysomnography. Sleep efficiency refers to the percentage of time a person sleeps, in relation to the amount of time a person spends in bed trying to sleep. The percentage is calculated by dividing the Total Sleep Time by the Total Time in Bed. |
| Sleep Quality | First morning after 8-h time in bed immediately following CFL/LED light exposure. | Self-reported sleep quality was assessed using a post sleep questionnaire. Score on subjective scale range 1-7, higher scores indicate higher sleep quality. |
| Subjective Alerting Response | 6-h constant posture interval of the light exposure. | Self-reported sleepiness measured during the light exposure using the Karolinska Sleepiness Scale (KSS). Range of scores 1-9, higher score indicate higher subjective sleepiness. Measures were taken hourly throughout the 6-hour constant posture interval of the light exposure and then averaged to calculate a single value per participant. |
| Objective Alerting Response | 6-h constant posture interval of the light exposure | Mean reaction time assessed using the 10-minute psychomotor vigilance test. Higher numbers indicate slower reaction times indicating less alertness. Measures were taken hourly throughout the 6-hour constant posture interval of the light exposure and then averaged to calculate a single value per participant. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Compact Fluorescent Light 90 Lux 90 lux exposure of a commercially available Compact Fluorescent Light (CFL).
Visible light: We will compare the effects of two light sources, equated for visual stimulus (lux), on multiple non-visual responses to light including melatonin suppression before bedtime. We will compare a 90 lux exposure of a commercially available Compact Fluorescent Light (CFL) with a novel LED white light source that is depleted in the short-wavelength visible range (Biological Illumination LCC, FL). | 8 |
| Blue-depleted LED Light 90 Lux 90 lux exposure of a novel LED white light source that is depleted in the short-wavelength visible range (Biological Illumination LCC, FL).
Visible light: We will compare the effects of two light sources, equated for visual stimulus (lux), on multiple non-visual responses to light including melatonin suppression before bedtime. We will compare a 90 lux exposure of a commercially available Compact Fluorescent Light (CFL) with a novel LED white light source that is depleted in the short-wavelength visible range (Biological Illumination LCC, FL). | 8 |
| Compact Fluorescent Light 50 Lux 50 lux exposure of a commercially available Compact Fluorescent Light (CFL).
Visible light: We will compare the effects of two light sources, equated for visual stimulus (lux), on multiple non-visual responses to light including melatonin suppression before bedtime. We will compare a 90 lux exposure of a commercially available Compact Fluorescent Light (CFL) with a novel LED white light source that is depleted in the short-wavelength visible range (Biological Illumination LCC, FL). | 8 |
| Blue-depleted LED Light 50 Lux 50 lux exposure of a novel LED white light source that is depleted in the short-wavelength visible range (Biological Illumination LCC, FL).
Visible light: We will compare the effects of two light sources, equated for visual stimulus (lux), on multiple non-visual responses to light including melatonin suppression before bedtime. We will compare a 90 lux exposure of a commercially available Compact Fluorescent Light (CFL) with a novel LED white light source that is depleted in the short-wavelength visible range (Biological Illumination LCC, FL). | 8 |
| Total | 32 |
Baseline characteristics
| Characteristic | Compact Fluorescent Light 90 Lux | Blue-depleted LED Light 90 Lux | Compact Fluorescent Light 50 Lux | Blue-depleted LED Light 50 Lux | Total |
|---|---|---|---|---|---|
| Age, Continuous | 25.0 years STANDARD_DEVIATION 1.9 | 24.3 years STANDARD_DEVIATION 3.2 | 23.6 years STANDARD_DEVIATION 3.1 | 24.8 years STANDARD_DEVIATION 3 | 24.4 years STANDARD_DEVIATION 2.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 8 Participants | 6 Participants | 7 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 2 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 6 Participants | 6 Participants | 4 Participants | 24 Participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 16 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 9 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 8 | 1 / 9 | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 9 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Melatonin Suppression
Melatonin suppression is measured as the percentage of melatonin AUC relative to the AUC measured in dim light on the previous day. AUC was calculated during the 6 h of light exposure and the corresponding 6-h interval 24 hours earlier. Higher values indicate more light-induced melatonin suppression.
Time frame: 6-h constant posture interval of the light exposure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Compact Fluorescent Light 90 Lux | Melatonin Suppression | 71.4 Percentage suppression | Standard Error 5.7 |
| Blue-depleted LED Light 90 Lux | Melatonin Suppression | 70.1 Percentage suppression | Standard Error 7.2 |
| Compact Fluorescent Light 50 Lux | Melatonin Suppression | 54.3 Percentage suppression | Standard Error 5.9 |
| Blue-depleted LED Light 50 Lux | Melatonin Suppression | 32.5 Percentage suppression | Standard Error 7.6 |
Comparison: Contrasting LED vs. CFL at 90 lux intensity. Melatonin suppression is measured as the percentage of melatonin AUC relative to the AUC measured in dim light on the previous day. Higher values indicate more light-induced melatonin suppression.p-value: 0.73t-test, 2 sided
Comparison: Contrasting LED vs. CFL at 50 lux intensityp-value: 0.001t-test, 2 sided
Secondary
Objective Alerting Response
Mean reaction time assessed using the 10-minute psychomotor vigilance test. Higher numbers indicate slower reaction times indicating less alertness. Measures were taken hourly throughout the 6-hour constant posture interval of the light exposure and then averaged to calculate a single value per participant.
Time frame: 6-h constant posture interval of the light exposure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Compact Fluorescent Light 90 Lux | Objective Alerting Response | 247.7 Millisecond | Standard Error 7.2 |
| Blue-depleted LED Light 90 Lux | Objective Alerting Response | 249.7 Millisecond | Standard Error 7.3 |
| Compact Fluorescent Light 50 Lux | Objective Alerting Response | 229.3 Millisecond | Standard Error 4.6 |
| Blue-depleted LED Light 50 Lux | Objective Alerting Response | 238.2 Millisecond | Standard Error 6.7 |
Secondary
Sleep Quality
Self-reported sleep quality was assessed using a post sleep questionnaire. Score on subjective scale range 1-7, higher scores indicate higher sleep quality.
Time frame: First morning after 8-h time in bed immediately following CFL/LED light exposure.
Population: Post-sleep questionnaires from two participants (each completing once in the Compact Fluorescent Light 90 lux condition and once in the Blue-depleted LED light 90 lux condition) were not collected due to technical error. As a result n=6 were available for data analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Compact Fluorescent Light 90 Lux | Sleep Quality | 4.5 Arbitrary units - scale score | Standard Error 0.2 |
| Blue-depleted LED Light 90 Lux | Sleep Quality | 4.6 Arbitrary units - scale score | Standard Error 0.2 |
| Compact Fluorescent Light 50 Lux | Sleep Quality | 4.8 Arbitrary units - scale score | Standard Error 0.3 |
| Blue-depleted LED Light 50 Lux | Sleep Quality | 4.8 Arbitrary units - scale score | Standard Error 0.2 |
Secondary
Sleep Structure
Sleep efficiency assessed by polysomnography. Sleep efficiency refers to the percentage of time a person sleeps, in relation to the amount of time a person spends in bed trying to sleep. The percentage is calculated by dividing the Total Sleep Time by the Total Time in Bed.
Time frame: 8-h time in bed immediately following CFL/LED light exposure.
Population: Due to limited financial resources and based on the results of the primary outcome of melatonin suppression in the 90-lux condition, we did not score the PSG data for sleep stage in the 90-lux condition and therefore could not perform an analysis of sleep efficiency. PSG data in one 50-lux condition participant was not collected due to equipment malfunction.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Compact Fluorescent Light 50 Lux | Sleep Structure | 91.5 % total sleep time of total time in bed | Standard Error 1 |
| Blue-depleted LED Light 50 Lux | Sleep Structure | 92.4 % total sleep time of total time in bed | Standard Error 1.1 |
p-value: 0.19t-test, 2 sided
Secondary
Subjective Alerting Response
Self-reported sleepiness measured during the light exposure using the Karolinska Sleepiness Scale (KSS). Range of scores 1-9, higher score indicate higher subjective sleepiness. Measures were taken hourly throughout the 6-hour constant posture interval of the light exposure and then averaged to calculate a single value per participant.
Time frame: 6-h constant posture interval of the light exposure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Compact Fluorescent Light 90 Lux | Subjective Alerting Response | 4.1 Score on a scale | Standard Error 0.2 |
| Blue-depleted LED Light 90 Lux | Subjective Alerting Response | 4.3 Score on a scale | Standard Error 0.3 |
| Compact Fluorescent Light 50 Lux | Subjective Alerting Response | 4.3 Score on a scale | Standard Error 0.3 |
| Blue-depleted LED Light 50 Lux | Subjective Alerting Response | 4.3 Score on a scale | Standard Error 0.3 |
p-value: 0.17t-test, 2 sided
p-value: 1t-test, 2 sided