Bright Light Therapy for Treatment of Sleep Problems Following Mild Traumatic Brain Injury

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02374918

Enrollment

Registered

2015-03-02

Start date

2014-12-31

Completion date

2019-12-31

Last updated

2021-06-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Concussion, Mild, Post-Concussion Symptoms, Sleep Problems

Keywords

Mild traumatic brain injury, Concussion, Sleep problems, Brain imaging, fMRI

Brief summary

The purpose of the research study is to understand the effectiveness of a six-week course of light exposure on cognitive functioning, mood, activity, and sleep in people that have suffered a head injury leading to a concussion.

Detailed description

Mild traumatic brain injuries (mTBI) or concussions are an increasingly prevalent injury in the investigators 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, the investigators 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. This study will also have a healthy control (HC)/effect localization arm that will assist in identifying and mapping the brain systems before and after light exposure so that researchers may develop further insights into the relationship between concussion, light exposure, sleep, and brain function. This healthy control arm will also provide brain targets for study in the analysis of the Main Study Arm.

Interventions

DEVICEmTBI wavelength-1 bright light

6 weeks of daily light exposure, 30 minutes per morning

DEVICEmTBI wavelength-2 bright light

6 weeks of daily light exposure, 30 minutes per morning

DEVICEHC wavelength-1 bright light

30 minutes of light exposure

DEVICEHC wavelength-2 bright light

30 minutes of light exposure

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 50 Years

Healthy volunteers

Yes

Inclusion criteria

* Age range between 18 and 50. * 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 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.) * Abnormal visual acuity that is not corrected by contact lenses * 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 and/or use of marijuana before the age of 16. 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.

Design outcomes

Primary

Measure	Time frame	Description
Sleep Quality - Pittsburgh Sleep Quality Index (PSQI)	Post 6-week intervention	The Pittsburgh Sleep Quality Index (PSQI) subscale measurement that was used is overall sleep quality, which is derived from question 6 on the assessment and uses a Likert scale of 0 to 3. A score of 0 represents very good sleep quality (better outcome), while a measurement of 3 represents very bad sleep quality (worse outcome).
Sleep Quality - Actigraphy Sleep Efficiency	Post 6-week intervention	Sleep Efficiency is the overall percentage of time that the participant was scored as sleeping during their night of sleep (range: 0-100%). Higher percentages suggest higher sleep quality and a better outcome.
Sleep Quality - Actigraphy Wake After Sleep Onset	Post 6-week intervention	Wake After Sleep Onset (WASO) is how many minutes the participant, during their night of sleep, was determined to be awake after their sleep onset. Sleep onset is defined as a state of at least 2 minutes of uninterrupted sleep. Higher values indicate a worse outcome (range: 1-125 minutes).
Executive Function Task - Multi-Source Interference Task (MSIT)	Post 6-week intervention	Neural activation during functional magnetic resonance imaging (fMRI) measuring executive functioning using the MSIT.
Performance on Neuropsychological Assessment - Automated Neuropsychological Assessment Metrics	Post 6-week intervention	The Automated Neuropsychological Assessment Metrics (ANAM) is a neuropsychological battery that uses individual tests to measure cognitive efficiency in areas including attention, concentration, reaction time, memory, processing speed, and decision making. Subscale scores are put in terms of a throughput score, which is calculated to be a ratio of correct responses per minute, as a way to measure cognitive efficiency in the participant; as such, the units for the throughput scores would be in terms of correct responses/minute. Higher throughput scores indicate increased levels of cognitive efficiency in the relevant subscale. The throughput score ranges for the ANAM subscales are: code substitution learning: 0-147 responses per minute procedural reaction time: 0-151 responses per minute mathematical processing: 0-145 responses per minute matching to sample: 0-97 responses per minute code substitution delayed: 0-155 responses per minute
Performance on Neuropsychological Assessment - Repeatable Battery for the Assessment of Neuropsychological Status	Post 6-week intervention	The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) uses all of its subscales to calculate the RBANS total score (index). To obtain the RBANS total score (index), the raw scores of the subtests must first be computed into index scores for their relevant subscale (different subtest raw scores feed into specific subscales) using RBANS specific tables that have scaled scores embedded and are normed for the age of the participant. The index scores of each subscale are then summed together to get the Sum of Index Scores, which has a possible range of 200-800. Once the Sum of Index Scores is found, the total score (index) is then found using another RBANS specific table with scaled scores embedded within it. The total score (index) has a possible range of 40-160, with a higher total score (index) is related to a better outcome.
Performance on Neuropsychological Assessment - Psychomotor Vigilance Task	Post 6-week intervention	The Psychomotor Vigilance Task (PVT) is a task that tests alertness by having the participant press a button every time they see a stimulus image appear on a screen. This image is presented at random 2-10 second intervals throughout the entirety of the task. The reaction time (RT) is one of the PVT measurements and is the time, measured in milliseconds, that it takes for the participant to view the stimulus image and then press the button, confirming that they have indeed viewed the stimulus image at that time. The PVT measures speed using the following equation: 1/RT \* 1000. The PVT measurement used here is average speed, so all the calculated speeds were then averaged over the entire trial period to obtain the final value for that trial at that time point (post-tx 1,2,3). Since the PVT is a timed measurement of reaction times, lower scores are considered 'better' or indicate an increased level of vigilance.
Daytime Sleepiness - Epworth Sleepiness Scale	Post 6-week intervention	The Epworth Sleepiness Scale (ESS) is an 8-item questionnaire that characterizes the likelihood of the participant 'dozing off' during typical daily activities over their last 2 weeks, and uses a 0-3 point Likert scale, where 0 corresponds to Would never doze and 3 corresponds to having a High chance of dozing during the activity in question. The ESS score is calculated by adding up all the scores for each question, which means that the ESS score has a range of 0-24, while a higher score indicates that the participant had more issues with daytime sleepiness (worse outcome).
Daytime Sleepiness - Functional Outcome of Sleep Questionnaire	Post 6-week intervention	The Functional Outcome of Sleep Questionnaire (FOSQ) questions 1-26 use a 1-4 (ordinal) likert (1 = No difficulty with sleepiness, 4 = Yes, extreme difficulty with sleepiness) and the participant also has the option of putting 0 = I don't do this activity for other reasons. FOSQ questions 27-30 use a 1-4 Likert scale where 1 = Very low in terms of characterizing the level that sleepiness affects different aspects of their intimate romantic relations, while a 4 = High amount of impact on their intimate romantic relations. The FOSQ total score measurement is determined by calculating the mean of all 5 subscale scores and then multiplying that value by 5 (range: 0-24). A higher score indicates that the participant had more issues with daytime sleepiness.
Post-Concussive Symptoms (Rivermead Post-Concussion Symptoms Questionnaire)	Post 6-week intervention	The Rivermead Post-Concussion Symptoms Questionnaire (RPCSQ) will be used to assess post-concussive symptoms related to sleep. All questions on the RPCSQ use a 0 to 4 Likert scale concerning the severity of experiencing differing symptoms, where 0 = not experienced and 4 = severe problem. As such, having a higher score is indicative that the participant is having more serious sleep issues related to their head injury. The RPCSQ subscale measurements that were used below are: RPQ3, which is the summed scores from the first 3 questions on the form, with the subscale total ranging from 0-12, and RPQ13, which is the summed scores from questions 4 to 16 on the form, with the subscale total ranging from 0-52. The RPQ3 subscale is associated with earlier symptom clusters of post-concussive symptoms as they relate to sleep disturbances, while the RPQ13 subscale is associated with later symptom clusters of post-concussive symptoms as they relate to sleep disturbances.

Countries

United States

Participant flow

Recruitment details

Participants were recruited from around the city of Tucson. The first participant was enrolled in December 2014. The Effect Localization Arm completed enrollment in April 2015 and the Treatment Arm completed enrollment in May 2019.

Pre-assignment details

No pre-assignment criteria were needed after enrollment but before study group assignment for the Effect Localization Arm. For the Treatment Arm, participants went through a screening visit before study group assignment and were excluded based on the inclusion/exclusion criteria.

Participants by arm

Arm	Count
mTBI Wavelength-1 Bright Light 30 minutes daily light exposure for 6 weeks mTBI wavelength-1 bright light: 6 weeks of daily light exposure, 30 minutes per morning	17
mTBI Wavelength-2 Bright Light 30 minutes daily light exposure for 6 weeks mTBI wavelength-2 bright light: 6 weeks of daily light exposure, 30 minutes per morning	18
HC Wavelength-1 Bright Light 30 minutes of light exposure HC wavelength-1 bright light: 30 minutes of light exposure	18
HC Wavelength-2 Bright Light 30 minutes of light exposure HC wavelength-2 bright light: 30 minutes of light exposure	18
Total	71

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Lack of Efficacy	0	0	1	1
Overall Study	Protocol Violation	2	0	2	1
Overall Study	Withdrawal by Subject	1	1	1	0

Baseline characteristics

Characteristic	mTBI Wavelength-2 Bright Light	mTBI Wavelength-1 Bright Light	Total	HC Wavelength-1 Bright Light	HC Wavelength-2 Bright Light
Actigraphy - Sleep Efficiency	80.98 Percentage of time asleep STANDARD_DEVIATION 4.71	82.53 Percentage of time asleep STANDARD_DEVIATION 4.83	81.73 Percentage of time asleep STANDARD_DEVIATION 4.63	—	—
Actigraphy - Wake After Sleep Onset (WASO)	11.97 Minutes STANDARD_DEVIATION 3.23	11.2 Minutes STANDARD_DEVIATION 3.02	11.60 Minutes STANDARD_DEVIATION 3.06	—	—
Age, Categorical <=18 years	1 Participants	3 Participants	7 Participants	1 Participants	2 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	17 Participants	14 Participants	64 Participants	17 Participants	16 Participants
Age, Continuous	26.23 years STANDARD_DEVIATION 7.62	25.53 years STANDARD_DEVIATION 8.65	23.95 years STANDARD_DEVIATION 6.41	21.61 years STANDARD_DEVIATION 2.86	22.28 years STANDARD_DEVIATION 4.03
ANAM Code Substitution delay - thruput score	52.88 correct responses/minute STANDARD_DEVIATION 8.72	41.06 correct responses/minute STANDARD_DEVIATION 13.11	46.8 correct responses/minute STANDARD_DEVIATION 11.96	—	—
ANAM Code Substitution Learning - thruput score	55.88 correct responses/minute STANDARD_DEVIATION 12.39	46.78 correct responses/minute STANDARD_DEVIATION 14.74	51.20 correct responses/minute STANDARD_DEVIATION 13.79	—	—
ANAM Matching to Sample - thruput score	33.29 correct responses/minute STANDARD_DEVIATION 11.55	29.5 correct responses/minute STANDARD_DEVIATION 8.05	31.34 correct responses/minute STANDARD_DEVIATION 9.86	—	—
ANAM Mathematical Processing - thruput score	21.18 correct responses/minute STANDARD_DEVIATION 7.38	17.89 correct responses/minute STANDARD_DEVIATION 8.44	19.49 correct responses/minute STANDARD_DEVIATION 7.89	—	—
ANAM Procedural Reaction Time - thruput score	97.06 correct responses/minute STANDARD_DEVIATION 19.41	86.83 correct responses/minute STANDARD_DEVIATION 19.55	95.26 correct responses/minute STANDARD_DEVIATION 17.98	—	—
ESS total score	8.18 units on a scale STANDARD_DEVIATION 3.28	8.72 units on a scale STANDARD_DEVIATION 3.32	8.46 units on a scale STANDARD_DEVIATION 3.27	—	—
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants	2 Participants	14 Participants	3 Participants	6 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants	15 Participants	57 Participants	15 Participants	12 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
FOSQ Total Score	15.37 units on a scale STANDARD_DEVIATION 3.82	17.10 units on a scale STANDARD_DEVIATION 2.18	14.06 units on a scale STANDARD_DEVIATION 10.86	—	—
Post-Concussive Symptoms - Rivermead Post-Concussion Symptoms Questionnaire RPQ13	15.9 units on a scale STANDARD_DEVIATION 8	12.3 units on a scale STANDARD_DEVIATION 13	14.1 units on a scale STANDARD_DEVIATION 10.9	—	—
Post-Concussive Symptoms - Rivermead Post-Concussion Symptoms Questionnaire RPQ3	3.5 units on a scale STANDARD_DEVIATION 2.5	3.3 units on a scale STANDARD_DEVIATION 3	3.4 units on a scale STANDARD_DEVIATION 2.7	—	—
PVT average speed - Run 1	3.52 responses/second STANDARD_DEVIATION 0.35	3.27 responses/second STANDARD_DEVIATION 0.41	3.39 responses/second STANDARD_DEVIATION 0.39	—	—
PVT average speed - Run 2	3.45 responses/second STANDARD_DEVIATION 0.42	3.22 responses/second STANDARD_DEVIATION 0.51	3.33 responses/second STANDARD_DEVIATION 0.48	—	—
PVT average speed - Run 3	3.50 responses/second STANDARD_DEVIATION 0.59	3.17 responses/second STANDARD_DEVIATION 0.43	3.33 responses/second STANDARD_DEVIATION 0.53	—	—
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	5 Participants	1 Participants	3 Participants
Race (NIH/OMB) Black or African American	1 Participants	0 Participants	1 Participants	0 Participants	0 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	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	2 Participants	2 Participants	0 Participants
Race (NIH/OMB) White	17 Participants	16 Participants	63 Participants	15 Participants	15 Participants
RBANS total score (index)	96.1 units on a scale STANDARD_DEVIATION 11.5	88.2 units on a scale STANDARD_DEVIATION 10	92.53 units on a scale STANDARD_DEVIATION 11.4	—	—
Region of Enrollment United States	18 participants	17 participants	67 participants	18 participants	18 participants
Sex: Female, Male Female	10 Participants	12 Participants	41 Participants	9 Participants	10 Participants
Sex: Female, Male Male	8 Participants	5 Participants	30 Participants	9 Participants	8 Participants
Sleep Quality - PSQI	1.76 units on a scale STANDARD_DEVIATION 0.66	1.44 units on a scale STANDARD_DEVIATION 0.7	1.60 units on a scale STANDARD_DEVIATION 0.69	—	—

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 / 17	0 / 18	0 / 22	0 / 20
other Total, other adverse events	0 / 17	0 / 18	0 / 22	0 / 20
serious Total, serious adverse events	0 / 17	0 / 18	0 / 22	0 / 20

Outcome results

Primary

Daytime Sleepiness - Epworth Sleepiness Scale

The Epworth Sleepiness Scale (ESS) is an 8-item questionnaire that characterizes the likelihood of the participant 'dozing off' during typical daily activities over their last 2 weeks, and uses a 0-3 point Likert scale, where 0 corresponds to Would never doze and 3 corresponds to having a High chance of dozing during the activity in question. The ESS score is calculated by adding up all the scores for each question, which means that the ESS score has a range of 0-24, while a higher score indicates that the participant had more issues with daytime sleepiness (worse outcome).