Traumatic Brain InjuryNCT03968874
Improving Sleep, Sleep-related Outcomes, and Biomarkers in Veterans
A study testing Light box therapy and Negative Ion Generator in people with Traumatic Brain Injury, run by Portland VA Medical Center at 1 site in United States.
Trial summary
The primary purpose of this project is to determine the effect of morning bright light therapy (MBLT) on sleep in Veterans with traumatic brain injury (TBI). Secondarily, the project aims to identify blood-based brain biomarkers (BBBM) associated with sleep in Veterans. Specific Aim 1. Read more about this study
- Who is it for?
- Ages 18 to 88 yearsHealthy volunteers can take part
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- Light box therapy and Negative Ion Generator
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 300 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2019to 1 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 88 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Veteran
- English-speaking
- Accessible by phone
Who cannot join
- Decisional impairment
- Macular degeneration
- Bipolar disorder
- Shift work
- Currently using lightbox or negative ion generator
Trial locations and contacts
1 site in 1 country.
About this study
The primary purpose of this project is to determine the effect of morning bright light therapy (MBLT) on sleep in Veterans with traumatic brain injury (TBI). Secondarily, the project aims to identify blood-based brain biomarkers (BBBM) associated with sleep in Veterans.
Specific Aim 1. Determine the effect of MBLT on sleep quality in Veterans (primary outcome).
Read more
Specific Aim 2. Determine the effect of MBLT on downstream effectors of improved sleep, including cognition, mood, and quality of life measures in Veterans (exploratory outcomes).
Specific Aim 3. Determine the effect of MBLT on levels of specific BBBM related to sleep, and whether changes in specific BBBM predict response to MBLT (secondary outcome).
This study can now be completed 100% remotely.
Read the detailed description
This project will utilize a biobehavioral intervention to improve sleep and apply a novel approach to measuring biomarkers in Veterans with TBI. The investigators will use morning bright light therapy (MBLT) to improve sleep. MBLT acts through intrinsically photosensitive retinal ganglion cells and has pleiotropic effects on sleep, circadian rhythms, cognition, mood, and pain through activation of brain circuits.
MBLT is a simple, cost-effective, home-based sleep intervention. It has been studied in a variety of neuropsychiatric populations, such as seasonal affective disorder, non-seasonal depression, Alzheimer's, Huntington's, Parkinson's disease, and schizophrenia. MBLT is an attractive intervention for TBI as patients typically report multiple concomitant symptoms including alterations in mood and alertness (daytime fatigue). One recent placebo-controlled study using MBLT reported improved fatigue in individuals with TBI. Moreover, MBLT has high patient acceptability and is scalable, owing to its ability to be rapidly implemented in any setting including in the home or in a rehabilitation facility.
To address the substantial limitation of using peripheral biomarkers to understand central pathophysiology in TBI, the investigators have developed a method to use blood-based brain biomarkers (BBBM) to track central pathophysiology and symptomatology of TBI and response to treatment. This method entails isolation of neuronally derived exosomes in peripheral blood. Exosomes are membrane bound structures that, instead of being delivered to lysosomes for destruction, reside in multivesicular bodies, fuse with the plasma membrane, and are exocytosed into extracellular spaces. Within the membrane of exosomes are various proteins present in the cell of origin; thus, the cargo of exosomes reflects the microenvironment from the site of exosome production. Exosomes hold promise in TBI since they can readily cross the blood brain barrier (BBB) and be isolated from peripheral circulation. Studying exosomes allows us to isolate those proteins that are routinely disrupted in patients with TBI and sleep disturbances, and to track changes in accordance with treatment condition over time.
In this project, the investigators will conduct a randomized controlled, single blinded trial in which Veterans with and without TBI will receive MBLT or modified negative ion generator; (see below for modification specifications) for 4-weeks. BBBM will be assessed in conjunction with MBLT/sham and neurobehavioral symptomatology. The investigators hypothesize that: 1) MBLT will be associated with improved sleep, and downstream effectors of improved sleep (i.e., cognition, mood, and quality of life), compared to the sham condition; 2) MBLT will show a correlation between BBBM and improved sleep, and levels of BBBM will predict those that respond to MBLT. This will provide novel insights into how these biomarkers relate to neuronal and behavioral changes following TBI and may inform trajectory of recovery.
The study can be completed 100% remotely, in person, or a combination of the two.
- Conditions
- Traumatic Brain Injury
- Being tested
- Light box therapy, Negative Ion Generator
- Keywords
- Veterans
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Light box therapyDevice
The intervention is sitting in front of a lightbox for 1 hour in the morning upon waking up.
Negative Ion GeneratorDevice
The intervention is sitting in front of a modified negative ion generator for 1 hour in the morning upon waking up.
| Study group | Role | What they receive |
|---|---|---|
| Light box | Experimental | Commercially available lightbox emitting 10,000 lux of light. Subjects asked to use lightbox everyday for an hour for 4 weeks upon waking. Receives: Device: Light box therapy |
| Negative Ion Generator | Sham comparator | Commercially available negative ion generator. Subjects asked to use everyday for an hour for 4 weeks upon waking. Receives: Device: Negative Ion Generator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Insomnia Severity Index (ISI)
Measures self-reported insomnia severity; total score range = 0-28 (higher total score = worse insomnia)
Measured: Baseline; after 4 weeks of intervention; and 2 months after the end of intervention
Secondary outcomes (1)
Change in NFL, GFAP, UCH-L1, and total tau
Change in neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and total tau
Measured: Baseline; after 4 weeks of intervention; and 2 months after the end of intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2019
- Study start1 Aug 2019
- Primary completion1 Dec 2027 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Portland VA Medical Center
- Sponsor type
- US federal agency
- Collaborators
- Center for Neuroscience and Regenerative Medicine (CNRM)
- Responsible party
- Principal investigator, Miranda M Lim, Portland VA Medical Center
- Investigators
- Miranda Lim, MD, PhD, Principal investigator, Portland VA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03968874
- Sponsor's protocol ID
- MIRB #4268, eIRB #19411
- Status last verified
- Sep 2026
- First submitted
- 23 May 2019
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All non-identifiable data will be made available to qualified researchers on request to the study PI.
Publications
Elliott JE, Brewer JS, Keil AT, Ligman BR, Bryant-Ekstrand MD, McBride AA, Powers K, Sicard SJ, Twamley EW, O'Neil ME, Hildebrand AD, Nguyen T, Morasco BJ, Gill JM, Dengler BA, Lim MM. Feasibility and acceptability for LION, a fully remote, randomized clinical trial within the VA for light therapy to improve sleep in Veterans with and without TBI: An MTBI2 sponsored protocol. PLoS One. 2025 Jan 7;20(1):e0305305. doi: 10.1371/journal.pone.0305305. eCollection 2025.
PubMed 39775195
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Sleep, Sleep-related Outcomes, and Biomarkers in Veterans
- ClinicalTrials.gov ID
- NCT03968874
- Acronym / sponsor ID
- MIRB #4268, eIRB #19411
- Conditions
- Traumatic Brain Injury
- Keywords
- Veterans
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Portland VA Medical CenterUS federal agency
- Collaborators
- Center for Neuroscience and Regenerative Medicine (CNRM)
- Study start
- 1 Aug 2019 (actual)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 30 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this project is to determine the effect of morning bright light therapy (MBLT) on sleep in Veterans with traumatic brain injury (TBI). Secondarily, the project aims to identify blood-based brain biomarkers (BBBM) associated with sleep in Veterans.
Specific Aim 1. Determine the effect of MBLT on sleep quality in Veterans (primary outcome).
Specific Aim 2. Determine the effect of MBLT on downstream effectors of improved sleep, including cognition, mood, and quality of life measures in Veterans (exploratory outcomes).
Specific Aim 3. Determine the effect of MBLT on levels of specific BBBM related to sleep, and whether changes in specific BBBM predict response to MBLT (secondary outcome).
This study can now be completed 100% remotely.
Detailed description
This project will utilize a biobehavioral intervention to improve sleep and apply a novel approach to measuring biomarkers in Veterans with TBI. The investigators will use morning bright light therapy (MBLT) to improve sleep. MBLT acts through intrinsically photosensitive retinal ganglion cells and has pleiotropic effects on sleep, circadian rhythms, cognition, mood, and pain through activation of brain circuits.
MBLT is a simple, cost-effective, home-based sleep intervention. It has been studied in a variety of neuropsychiatric populations, such as seasonal affective disorder, non-seasonal depression, Alzheimer's, Huntington's, Parkinson's disease, and schizophrenia. MBLT is an attractive intervention for TBI as patients typically report multiple concomitant symptoms including alterations in mood and alertness (daytime fatigue). One recent placebo-controlled study using MBLT reported improved fatigue in individuals with TBI. Moreover, MBLT has high patient acceptability and is scalable, owing to its ability to be rapidly implemented in any setting including in the home or in a rehabilitation facility.
To address the substantial limitation of using peripheral biomarkers to understand central pathophysiology in TBI, the investigators have developed a method to use blood-based brain biomarkers (BBBM) to track central pathophysiology and symptomatology of TBI and response to treatment. This method entails isolation of neuronally derived exosomes in peripheral blood. Exosomes are membrane bound structures that, instead of being delivered to lysosomes for destruction, reside in multivesicular bodies, fuse with the plasma membrane, and are exocytosed into extracellular spaces. Within the membrane of exosomes are various proteins present in the cell of origin; thus, the cargo of exosomes reflects the microenvironment from the site of exosome production. Exosomes hold promise in TBI since they can readily cross the blood brain barrier (BBB) and be isolated from peripheral circulation. Studying exosomes allows us to isolate those proteins that are routinely disrupted in patients with TBI and sleep disturbances, and to track changes in accordance with treatment condition over time.
In this project, the investigators will conduct a randomized controlled, single blinded trial in which Veterans with and without TBI will receive MBLT or modified negative ion generator; (see below for modification specifications) for 4-weeks. BBBM will be assessed in conjunction with MBLT/sham and neurobehavioral symptomatology. The investigators hypothesize that: 1) MBLT will be associated with improved sleep, and downstream effectors of improved sleep (i.e., cognition, mood, and quality of life), compared to the sham condition; 2) MBLT will show a correlation between BBBM and improved sleep, and levels of BBBM will predict those that respond to MBLT. This will provide novel insights into how these biomarkers relate to neuronal and behavioral changes following TBI and may inform trajectory of recovery.
The study can be completed 100% remotely, in person, or a combination of the two.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Light box | Experimental | Device: Light box therapyCommercially available lightbox emitting 10,000 lux of light. Subjects asked to use lightbox everyday for an hour for 4 weeks upon waking. |
| Negative Ion Generator | Sham comparator | Device: Negative Ion GeneratorCommercially available negative ion generator. Subjects asked to use everyday for an hour for 4 weeks upon waking. |
Who may qualify
- Ages
- 18 to 88 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Veteran
- English-speaking
- Accessible by phone
Key exclusion criteria (5 listed)
- Decisional impairment
- Macular degeneration
- Bipolar disorder
- Shift work
- Currently using lightbox or negative ion generator
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Light box therapyThe intervention is sitting in front of a lightbox for 1 hour in the morning upon waking up. | Device | Light box |
| Negative Ion GeneratorThe intervention is sitting in front of a modified negative ion generator for 1 hour in the morning upon waking up. | Device | Negative Ion Generator |
Primary outcome
Change in Insomnia Severity Index (ISI)
Time frame: Baseline; after 4 weeks of intervention; and 2 months after the end of intervention
Measures self-reported insomnia severity; total score range = 0-28 (higher total score = worse insomnia)
1 secondary outcome
Change in NFL, GFAP, UCH-L1, and total tau
Time frame: Baseline; after 4 weeks of intervention; and 2 months after the end of intervention
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2026.
- Derived from this study: PubMed 39775195Elliott JE, Brewer JS, Keil AT, Ligman BR, Bryant-Ekstrand MD, McBride AA, Powers K, Sicard SJ, Twamley EW, O'Neil ME, Hildebrand AD, Nguyen T, Morasco BJ, Gill JM, Dengler BA, Lim MM. Feasibility and acceptability for LION, a fully remote, randomized clinical trial within the VA for light therapy to improve sleep in Veterans with and without TBI: An MTBI2 sponsored protocol. PLoS One. 2025 Jan 7;20(1):e0305305. doi: 10.1371/journal.pone.0305305. eCollection 2025.
- Individual participant dataSharing planned: Yes. All non-identifiable data will be made available to qualified researchers on request to the study PI.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Miranda Lim, MD, PhD principal investigator
Portland VA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Light box therapy and Negative Ion Generator in people with Traumatic Brain Injury, run by Portland VA Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 17 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Insomnia Severity Index (ISI) (time frame: Baseline; after 4 weeks of intervention; and 2 months after the end of intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03968874, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2026.