Improving Sleep, Sleep-related Outcomes, and Biomarkers in Veterans
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03968874|
Recruitment Status : Recruiting
First Posted : May 30, 2019
Last Update Posted : April 12, 2022
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.
|Condition or disease||Intervention/treatment||Phase|
|Traumatic Brain Injury||Device: Light box therapy Device: Negative Ion Generator||Not Applicable|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||300 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||Improving Sleep, Sleep-related Outcomes, and Biomarkers in Veterans|
|Actual Study Start Date :||August 1, 2019|
|Estimated Primary Completion Date :||August 1, 2024|
|Estimated Study Completion Date :||August 1, 2025|
Experimental: Light box
Commercially available lightbox emitting 10,000 lux of light. Subjects asked to use lightbox everyday for an hour for 4 weeks upon waking.
Device: Light box therapy
The intervention is sitting in front of a lightbox for 1 hour in the morning upon waking up.
Sham Comparator: Negative Ion Generator
Commercially available negative ion generator. Subjects asked to use everyday for an hour for 4 weeks upon waking.
Device: Negative Ion Generator
The intervention is sitting in front of a modified negative ion generator for 1 hour in the morning upon waking up.
- 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)
- 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 ]Change in neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and total tau
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03968874
|Contact: Miranda Lim, MD, PhD||503-220-8262 ext firstname.lastname@example.org|
|United States, Oregon|
|Portland VA Medical Center||Recruiting|
|Portland, Oregon, United States, 97239|
|Contact: Miranda M Lim, MD, PhD email@example.com|
|Principal Investigator:||Miranda Lim, MD, PhD||Portland VA|