Effects of Bright Light Therapy in Mild Traumatic Brain Injury

• Sponsor: University of Arizona (Other)
• Overall Status: Completed
• CT.gov ID: NCT01747811
• Collaborator: U.S. Army Medical Research Acquisition Activity (U.S. Fed)
• Enrollment: 32
• Location: 1
• Arms: 2
• Duration (Months): 36
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

Mild traumatic brain injuries (mTBI) or "concussions" are an increasingly prevalent injury in our society. Patients with post-concussion syndrome have been shown to have deficits on tests of short term memory, divided attention, multi-tasking, information processing speed, and reaction time, as well as alteration in mood and emotional functioning. Many patients have other vague complaints including fatigue, dizziness, irritability, sleep disturbances, and chronic headaches. Furthermore, sleep disruption of one of the most common complaints in patients suffering from traumatic brain injuries, with as many as 40 to 65% of patients with mTBI complaining of insomnia. Sleep problems in these patients are associated with poorer outcome, while resolution of the sleep disturbance is associated with improvement in cognitive functioning.

Despite recent evidence of the correlation between sleep quality and recovery from traumatic brain injury, and the well-established role of sleep in neural plasticity and neurogenesis, there have been virtually no direct studies of the causal effects of sleep on recovery following mTBI. However, it is quite likely that sleep plays a critical role in recovery following brain injury.

A particularly promising non-pharmacologic approach that shows potential in improving/modifying abnormalities of the circadian rhythm and sleep-wake schedule is bright light therapy. For the proposed investigation, we hypothesize that bright light therapy may be helpful in improving the sleep of patients with a recent history of mTBI and may also have other mood elevating effects, both of which should promote positive treatment outcome in these individuals. Bright light therapy may increase the likelihood that they will recover more quickly, benefit more extensively from other forms of therapy, and build emotional and cognitive resilience.

Condition or Disease	Intervention/Treatment	Phase
Concussion, Mild; Post-Concussion Symptoms; Sleep Problems	Device: wavelength-1 bright light; Device: wavelength-2 bright light	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of Bright Light Therapy of Sleep, Cognition, Brain Function, and Neurochemistry in Mild Traumatic Brain Injury
• Study Start Date: Dec 1, 2010
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: wavelength-1 bright light 30 minutes daily light exposure for 6 weeks	Device: wavelength-1 bright light; 6 weeks of daily light exposure, 30 minutes per morning; Other Names: Philips goLITE energy light
Placebo Comparator: wavelength-2 bright light 30 minutes daily light exposure for 6 weeks	Device: wavelength-2 bright light; 6 weeks of daily light exposure, 30 minutes per morning; Other Names: Philips goLITE energy light

Outcome Measures

Primary Outcome Measures

1. Performance on Multiple Sleep Latency Test (MSLT) [Change from baseline performance at 6 weeks (post-treatment)]

   The MSLT is a objective measure of sleepiness. Participants will take a brief nap 3 times during the 1st and second visit. The period of time between wake and sleep onset will be utilized as an objective measure of sleepiness (in minutes). A mean value will be calculated for the entirety of the pre-treatment napping periods and for the post treatment visits.

Secondary Outcome Measures

1. Neural Activation During Functional Magnetic Resonance Imaging (fMRI) Executive Function Task [Change from baseline performance at 6 weeks (post-treatment)]

   Change from baseline in left prefrontal cortical response during a multi source interference task at six weeks. Methods utilized to assess activity in the left prefrontal cortex/inferior frontal operculum included a regions of interest analysis.

2. Score on Pittsburgh Sleep Quality Index (PSQI) [Change from baseline at 6 weeks (post-treatment)]

   The Pittsburgh Sleep Quality Index is a self report measure of sleep quality. The overall score takes into account many different facets of sleep, such as sleep quality, sleep latency, sleep duration, sleep disturbances, etc. The scores range from 0-21, and any score that is equal to or greater than 5 is indicative of poor sleep quality.

3. Actigraphy-measured Sleep Quality [Change from baseline at 6 weeks (post-treatment)]

   Actigraphy is an objective measure that determines sleep vs. wake. It is a watch with an accelerometer worn on the wrist. Sleep quality is determined by the amount of time in bed divided by the amount of time sleeping (in minutes).

4. Performance on Neuropsychological Assessment [Change from baseline at 6 weeks (post-treatment)]

   The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a neuropsychological assessment that measures different facets of memory including the following: immediate memory, visuospatial/constructional, language, attention, and delayed memory. This is given to all participants on both pre and post treatment visits. The total range for this scale is 40-160. Lower values represent a worse outcome, and higher values represent an improved outcome.

Other Outcome Measures

1. Change From Baseline in Beck Depression Inventory (BDI-II) Scores at 6 Weeks [Change from baseline at 6 weeks (post-treatment)]

   The Beck Depression Inventory (BDI-II) is a self report scale utilized for measuring the severity of depression. Scores can range from 0-63 (0 meaning minimal depressive symptoms, and 63 being severe depressive symptoms). Participants are given this on baseline and post treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Age range between 18 and 50.

• Subjects must be right handed.

• The primary language of the subjects must be English.

• Subjects have experienced a "concussion" or mTBI within the preceding 18 months, but no sooner that 4 weeks prior to their screening. The occurrence of a concussion or mTBI must be documented by a medical report or other professional witness documentation.

• If documented, Glasgow Coma Scale in the range of 13-15 following the injury.

• Subjects must have complaints of sleep difficulties that emerged or worsened following the most recent head injury.

• At least half of subjects must have evidence of sleep onset insomnia or delayed sleep phase disorder.

Exclusion Criteria:

• Any other history of neurological illness, current Diagnostic and Statistical Manual (DSM-IV) Axis I disorder, lifetime history of psychotic disorder, or head injury with loss of consciousness > 30 minutes

• Complicating medical conditions that may influence the outcome of neuropsychological assessment or functional imaging (e.g., HIV, brain tumor, etc.)

• Mixed or left-handedness

• Abnormal visual acuity that is not corrected by contact lenses

• Contraindicated conditions noted by the manufacture of the light device such as the use of photosynthesizing medications, history of cataract surgery, and pre-existing eye conditions.

• Metal within the body, claustrophobia, or other contraindications for neuroimaging

• Less than 9th grade education

• Excess current alcohol use (more than 2 instances of intake of 5+ drinks (men) when or 4+ drinks (women) when drinking in the past two months, and/or on average drinking > 2 drinks per day (men); > 1 drinks per day (women) during the past two months

• History of alcoholism or substance use disorder

• Significant use of illicit drugs

• History of marijuana use within the past 6 weeks, use of marijuana before the age of 16, and/or use of > 20 marijuana cigarettes throughout the participant's lifetime.

• Subjects who engage in shift-work, night work, or who have substantially desynchronized work-sleep schedules (i.e., sleeping later than 10:00 a.m. more than once a week) will be excluded

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona Medical Center	Tucson	Arizona	United States	85724

Sponsors and Collaborators

• University of Arizona
• U.S. Army Medical Research Acquisition Activity

Investigators

• Principal Investigator: William D Killgore, PhD, University of Arizona

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: William D. Killgore, Professor, University of Arizona
• ClinicalTrials.gov Identifier: NCT01747811
• Other Study ID Numbers: 2010-P-001570/1
• First Posted: Dec 12, 2012
• Last Update Posted: Jun 1, 2017
• Last Verified: May 1, 2017

• Keywords provided by William D. Killgore, Professor, University of Arizona: Mild traumatic brain injury; Concussion; Sleep problems; brain imaging; functional magnetic resonance imaging (FMRI)
• Additional relevant MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Brain Concussion; Dyssomnias; Parasomnias; Post-Concussion Syndrome

Study Results

Participant Flow

Arm/Group Title	Wavelength-1 Bright Light	Wavelength-2 Bright Light
Arm/Group Description	30 minutes daily light exposure for 6 weeks	30 minutes daily light exposure for 6 weeks
Period Title: Overall Study
STARTED	16	16
COMPLETED	14	12
NOT COMPLETED	2	4

Baseline Characteristics

Arm/Group Title	Wavelength-1 Bright Light	Wavelength-2 Bright Light	Total
Arm/Group Description	30 minutes daily light exposure for 6 weeks wavelength-1 bright light: 6 weeks of daily light exposure, 30 minutes per morning	30 minutes daily light exposure for 6 weeks	Total of all reporting groups
Overall Participants	14	12	26
Age (Count of Participants)
<=18 years	0 0%	2 16.7%	2 7.7%
Between 18 and 65 years	14 100%	10 83.3%	24 92.3%
>=65 years	0 0%	0 0%	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	23.07 (7.50)	23.46 (8.64)	23.24 (7.85)
Sex: Female, Male (Count of Participants)
Female	9 64.3%	6 50%	15 57.7%
Male	5 35.7%	6 50%	11 42.3%
Region of Enrollment (participants) [Number]
United States	14 100%	12 100%	26 100%

Outcome Measures

1. Primary Outcome

Title	Performance on Multiple Sleep Latency Test (MSLT)
Description	The MSLT is a objective measure of sleepiness. Participants will take a brief nap 3 times during the 1st and second visit. The period of time between wake and sleep onset will be utilized as an objective measure of sleepiness (in minutes). A mean value will be calculated for the entirety of the pre-treatment napping periods and for the post treatment visits.
Time Frame	Change from baseline performance at 6 weeks (post-treatment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Wavelength-1 Bright Light	Wavelength-2 Bright Light
Arm/Group Description	30 minutes daily light exposure for 6 weeks wavelength-1 bright light: 6 weeks of daily light exposure, 30 minutes per morning	30 minutes daily light exposure for 6 weeks
Measure Participants	14	12
MSLT_PreTreatment_Sleep Onset Latency (SOL)	6.67 (3.91)	7.32 (5.41)
MSLT_PostTreatment_Sleep Onset Latency (SOL)	6.73 (5.98)	7.88 (5.83)

2. Secondary Outcome

Title	Neural Activation During Functional Magnetic Resonance Imaging (fMRI) Executive Function Task
Description	Change from baseline in left prefrontal cortical response during a multi source interference task at six weeks. Methods utilized to assess activity in the left prefrontal cortex/inferior frontal operculum included a regions of interest analysis.
Time Frame	Change from baseline performance at 6 weeks (post-treatment)

Outcome Measure Data

Analysis Population Description

A total of 22 participants had useable data, 4 participants were excluded due to movement in the images.

Arm/Group Title	Wavelength-1 Bright Light	Wavelength-2 Bright Light
Arm/Group Description	30 minutes daily light exposure for 6 weeks wavelength-1 bright light: 6 weeks of daily light exposure, 30 minutes per morning	30 minutes daily light exposure for 6 weeks wavelength-2 bright light: 6 weeks of daily light exposure, 30 minutes per morning
Measure Participants	13	9
Mean (Standard Deviation) [Percent Signal Change]	0.098 (0.106)	-0.025 (0.25)

3. Secondary Outcome

Title	Score on Pittsburgh Sleep Quality Index (PSQI)
Description	The Pittsburgh Sleep Quality Index is a self report measure of sleep quality. The overall score takes into account many different facets of sleep, such as sleep quality, sleep latency, sleep duration, sleep disturbances, etc. The scores range from 0-21, and any score that is equal to or greater than 5 is indicative of poor sleep quality.
Time Frame	Change from baseline at 6 weeks (post-treatment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Wavelength-1 Bright Light	Wavelength-2 Bright Light
Arm/Group Description	30 minutes daily light exposure for 6 weeks	30 minutes daily light exposure for 6 weeks
Measure Participants	14	12
Pittsburgh Sleep Quality Index_Mean_PreTreatment	6.50 (2.14)	8.25 (1.60)
Pittsburgh Sleep Quality Index_Mean_PostTreatment	4.79 (2.29)	6.25 (3.19)

4. Secondary Outcome

Title	Actigraphy-measured Sleep Quality
Description	Actigraphy is an objective measure that determines sleep vs. wake. It is a watch with an accelerometer worn on the wrist. Sleep quality is determined by the amount of time in bed divided by the amount of time sleeping (in minutes).
Time Frame	Change from baseline at 6 weeks (post-treatment)

Outcome Measure Data

Analysis Population Description

We collected usable actigraphy from 29 participants. The 7 remaining participants had unusable actigraphy data.

Arm/Group Title	Wavelength-1 Bright Light	Wavelength-2 Bright Light
Arm/Group Description	30 minutes daily light exposure for 6 weeks wavelength-1 bright light: 6 weeks of daily light exposure, 30 minutes per morning	30 minutes daily light exposure for 6 weeks wavelength-2 bright light: 6 weeks of daily light exposure, 30 minutes per morning
Measure Participants	14	12
Mean (Standard Deviation) [minutes]	86.17 (1.60)	85.70 (5.21)

5. Secondary Outcome

Title	Performance on Neuropsychological Assessment
Description	The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a neuropsychological assessment that measures different facets of memory including the following: immediate memory, visuospatial/constructional, language, attention, and delayed memory. This is given to all participants on both pre and post treatment visits. The total range for this scale is 40-160. Lower values represent a worse outcome, and higher values represent an improved outcome.
Time Frame	Change from baseline at 6 weeks (post-treatment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Wavelength-1 Bright Light	Wavelength-2 Bright Light
Arm/Group Description	30 minutes daily light exposure for 6 weeks wavelength-1 bright light: 6 weeks of daily light exposure, 30 minutes per morning	30 minutes daily light exposure for 6 weeks
Measure Participants	14	12
Pre-treatment	102.71 (9.55)	101.67 (19.01)
Post Treatment	98.50 (9.20)	95.33 (15.39)

6. Other Pre-specified Outcome

Title	Change From Baseline in Beck Depression Inventory (BDI-II) Scores at 6 Weeks
Description	The Beck Depression Inventory (BDI-II) is a self report scale utilized for measuring the severity of depression. Scores can range from 0-63 (0 meaning minimal depressive symptoms, and 63 being severe depressive symptoms). Participants are given this on baseline and post treatment.
Time Frame	Change from baseline at 6 weeks (post-treatment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Wavelength-1 Bright Light	Wavelength-2 Bright Light
Arm/Group Description	30 minutes daily light exposure for 6 weeks	30 minutes daily light exposure for 6 weeks
Measure Participants	14	12
Mean (Standard Deviation) [units on a scale]	4.00 (5.07)	4.83 (3.88)

Adverse Events

Adverse Event Reporting Description	No serious or adverse events occurred during the course of the study.
Arm/Group Title	Wavelength-1 Bright Light		Wavelength-2 Bright Light
Arm/Group Description	30 minutes daily light exposure for 6 weeks		30 minutes daily light exposure for 6 weeks
All Cause Mortality
	Wavelength-1 Bright Light		Wavelength-2 Bright Light
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Wavelength-1 Bright Light		Wavelength-2 Bright Light
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Wavelength-1 Bright Light		Wavelength-2 Bright Light
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.