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

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.

Study Overview

• Status: Recruiting
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Device: Light box therapy; Device: Negative Ion Generator

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 Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Miranda Lim, MD, PhD; Phone Number: 57404 503-220-8262; Email: lmir@ohsu.edu

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Portland VA Medical Center
      • Contact: Miranda M Lim, MD, PhD; Email: lmir@ohsu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 88 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Portland VA Medical Center
• Collaborators: Center for Neuroscience and Regenerative Medicine (CNRM)
• Investigators: Principal Investigator: Miranda Lim, MD, PhD, Portland VA

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2019
• Primary Completion (ANTICIPATED): August 1, 2024
• Study Completion (ANTICIPATED): August 1, 2025

Study Registration Dates

• First Submitted: May 23, 2019
• First Submitted That Met QC Criteria: May 28, 2019
• First Posted (ACTUAL): May 30, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 12, 2022
• Last Update Submitted That Met QC Criteria: April 4, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Veterans
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: MIRB #4268, eIRB #19411

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All non-identifiable data will be made available to qualified researchers on request to the study PI.
• IPD Sharing Time Frame: Information will be sent as soon as is practical and will be available as long as the PI is available.
• IPD Sharing Access Criteria: Legitimate research agenda, including but not limited to request to double-check presented or published results and novel analyses.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No