Concussion, Mild, Post-Concussion Symptoms, Sleep Problems
Conditions
Keywords
Mild traumatic brain injury, Concussion, Sleep problems, brain imaging, functional magnetic resonance imaging (FMRI)
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.
Interventions
DEVICEwavelength-1 bright light
6 weeks of daily light exposure, 30 minutes per morning
DEVICEwavelength-2 bright light
6 weeks of daily light exposure, 30 minutes per morning
Sponsors
U.S. Army Medical Research Acquisition Activity
University of Arizona
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. * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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). |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Wavelength-1 Bright Light 30 minutes daily light exposure for 6 weeks
wavelength-1 bright light: 6 weeks of daily light exposure, 30 minutes per morning | 14 |
| Wavelength-2 Bright Light 30 minutes daily light exposure for 6 weeks | 12 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 2 | 4 |
Baseline characteristics
| Characteristic | Wavelength-2 Bright Light | Wavelength-1 Bright Light | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 14 Participants | 24 Participants |
| Age, Continuous | 23.46 Years STANDARD_DEVIATION 8.64 | 23.07 Years STANDARD_DEVIATION 7.5 | 23.24 Years STANDARD_DEVIATION 7.85 |
| Region of Enrollment United States | 12 participants | 14 participants | 26 participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 15 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 16 | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Performance on Multiple Sleep Latency Test (MSLT)
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)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Wavelength-1 Bright Light | Performance on Multiple Sleep Latency Test (MSLT) | MSLT_PreTreatment_Sleep Onset Latency (SOL) | 6.67 minutes | Standard Deviation 3.91 |
| Wavelength-1 Bright Light | Performance on Multiple Sleep Latency Test (MSLT) | MSLT_PostTreatment_Sleep Onset Latency (SOL) | 6.73 minutes | Standard Deviation 5.98 |
| Wavelength-2 Bright Light | Performance on Multiple Sleep Latency Test (MSLT) | MSLT_PreTreatment_Sleep Onset Latency (SOL) | 7.32 minutes | Standard Deviation 5.41 |
| Wavelength-2 Bright Light | Performance on Multiple Sleep Latency Test (MSLT) | MSLT_PostTreatment_Sleep Onset Latency (SOL) | 7.88 minutes | Standard Deviation 5.83 |
Secondary
Actigraphy-measured Sleep Quality
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)
Population: We collected usable actigraphy from 29 participants. The 7 remaining participants had unusable actigraphy data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Wavelength-1 Bright Light | Actigraphy-measured Sleep Quality | 86.17 minutes | Standard Deviation 1.6 |
| Wavelength-2 Bright Light | Actigraphy-measured Sleep Quality | 85.70 minutes | Standard Deviation 5.21 |
Secondary
Neural Activation During Functional Magnetic Resonance Imaging (fMRI) Executive Function Task
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)
Population: A total of 22 participants had useable data, 4 participants were excluded due to movement in the images.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Wavelength-1 Bright Light | Neural Activation During Functional Magnetic Resonance Imaging (fMRI) Executive Function Task | 0.098 Percent Signal Change | Standard Deviation 0.106 |
| Wavelength-2 Bright Light | Neural Activation During Functional Magnetic Resonance Imaging (fMRI) Executive Function Task | -0.025 Percent Signal Change | Standard Deviation 0.25 |
Secondary
Performance on Neuropsychological Assessment
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)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Wavelength-1 Bright Light | Performance on Neuropsychological Assessment | Pre-treatment | 102.71 units on a scale | Standard Deviation 9.55 |
| Wavelength-1 Bright Light | Performance on Neuropsychological Assessment | Post Treatment | 98.50 units on a scale | Standard Deviation 9.2 |
| Wavelength-2 Bright Light | Performance on Neuropsychological Assessment | Pre-treatment | 101.67 units on a scale | Standard Deviation 19.01 |
| Wavelength-2 Bright Light | Performance on Neuropsychological Assessment | Post Treatment | 95.33 units on a scale | Standard Deviation 15.39 |
Secondary
Score on Pittsburgh Sleep Quality Index (PSQI)
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)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Wavelength-1 Bright Light | Score on Pittsburgh Sleep Quality Index (PSQI) | Pittsburgh Sleep Quality Index_Mean_PreTreatment | 6.50 units on a scale | Standard Deviation 2.14 |
| Wavelength-1 Bright Light | Score on Pittsburgh Sleep Quality Index (PSQI) | Pittsburgh Sleep Quality Index_Mean_PostTreatment | 4.79 units on a scale | Standard Deviation 2.29 |
| Wavelength-2 Bright Light | Score on Pittsburgh Sleep Quality Index (PSQI) | Pittsburgh Sleep Quality Index_Mean_PreTreatment | 8.25 units on a scale | Standard Deviation 1.6 |
| Wavelength-2 Bright Light | Score on Pittsburgh Sleep Quality Index (PSQI) | Pittsburgh Sleep Quality Index_Mean_PostTreatment | 6.25 units on a scale | Standard Deviation 3.19 |
Other Pre-specified
Change From Baseline in Beck Depression Inventory (BDI-II) Scores at 6 Weeks
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)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Wavelength-1 Bright Light | Change From Baseline in Beck Depression Inventory (BDI-II) Scores at 6 Weeks | 4.00 units on a scale | Standard Deviation 5.07 |
| Wavelength-2 Bright Light | Change From Baseline in Beck Depression Inventory (BDI-II) Scores at 6 Weeks | 4.83 units on a scale | Standard Deviation 3.88 |