Improving Sleep, Sleep-related Outcomes, and Biomarkers in Veterans

Traumatic Brain Injury Clinical Trial

Official title:

Improving Sleep, Sleep-related Outcomes, and Biomarkers in Veterans

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03968874
• Other study ID #: MIRB #4268, eIRB #19411
• Status: Recruiting
• Phase: N/A
• Start date: August 1, 2019
• Est. completion date: August 1, 2025

Study information

• Verified date: April 2022
• Source: Portland VA Medical Center
• Contact: Miranda Lim, MD, PhD
• Phone: 503-220-8262
• Email: lmir[@]ohsu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: August 1, 2025
• Est. primary completion date: August 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 88 Years

Eligibility

Inclusion Criteria:

• Veteran

• English-speaking

• Accessible by phone

Exclusion Criteria:

• Decisional impairment

• Macular degeneration

• Bipolar disorder

• Shift work

• Currently using lightbox or negative ion generator

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Traumatic Brain Injury

Intervention

Device:
• Light box therapy
The intervention is sitting in front of a lightbox for 1 hour in the morning upon waking up.
• Negative Ion Generator
The intervention is sitting in front of a modified negative ion generator for 1 hour in the morning upon waking up.

Locations

Country	Name	City	State
United States	Portland VA Medical Center	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
Portland VA Medical Center	Center for Neuroscience and Regenerative Medicine (CNRM)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Insomnia Severity Index (ISI)	Measures self-reported insomnia severity; total score range = 0-28 (higher total score = worse insomnia)	Baseline; after 4 weeks of intervention; and 2 months after the end of intervention
Secondary	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	Baseline; after 4 weeks of intervention; and 2 months after the end of intervention