# Enhancing Precision Sleep Medicine in traumatic Brain Injury: Examining the feasibility of Home-Based Measurement of Circadian Timing

> **NIH VA I21** · VA EASTERN COLORADO HEALTH CARE SYSTEM · 2023 · —

## Abstract

Veterans with traumatic brain injury (TBI) frequently experience insomnia, which is linked with delayed TBI
recovery, more severe functional impairment, and exacerbation of disabling TBI sequelae such as depression,
chronic pain, and fatigue. Current research suggests that TBI can impact numerous systems involved in sleep
regulation, suggesting that insomnia may manifest from various etiologies and that a “one-size-fits-all”
approach to treatment is likely inadequate. As such, it is necessary to differentiate Veterans who may benefit
from standard evidence-based treatments, such as Cognitive Behavior Therapy for Insomnia, from those who
may require enhanced treatments targeting specific underlying mechanisms.
 An emerging body of evidence has established a link between circadian rhythm disruption and post-TBI
insomnia. A mismatch between circadian and desired sleep timing (i.e., “circadian misalignment”) is common
following TBI, as evidenced by perturbations of key circadian rhythms involved in sleep regulation (e.g.,
melatonin production), as well as the manifestation of circadian rhythm sleep-wake disorders. Importantly,
circadian-driven sleep disturbances require specialized treatments that target circadian rhythms (i.e.,
“chronotherapies”), such as timed sleep windows or enhanced light exposure, as standard treatment
approaches can fail to address or even exacerbate the underlying circadian misalignment. Thus,
circadian misalignment represents a novel and modifiable treatment target and has the potential to
improve functional outcomes in Veterans with TBI and insomnia.
 Detection of circadian misalignment and optimal use of chronotherapies require the ability to measure
circadian phase (i.e., timing of the central circadian clock). However, current sleep medicine in TBI is
hampered by a lack of pragmatic options for measuring circadian phase. This is because laboratory dim
light melatonin onset (DLMO), the gold standard measure of circadian phase, is time and cost prohibitive,
requiring specialized sample (e.g., saliva) collection facilities and placing substantial burden on the patient.
Recently, novel methods of DLMO measurement have been developed that may enhance the accessibility and
practicality of circadian phase assessment, although, as of yet, they have not been used in Veterans with TBI.
The proposed single-arm, longitudinal study seeks to evaluate the feasibility of two methods of
measuring DLMO in the home environment of Veterans with TBI and insomnia: 1) direct measurement
of self-collected salivary melatonin; and 2) indirect estimation of DLMO using activity and light-
exposure data collected through actigraphy. Additionally, this study seeks to explore the relationships
between circadian misalignment, sleep disturbance, and functional impairment in Veterans with TBI.
 The specific aims of this study are to: Aim 1) evaluate the feasibility of two methods of home DLMO
measurement (i.e., self-collected salivary melatonin and actig...

## Key facts

- **NIH application ID:** 10700406
- **Project number:** 1I21RX004414-01A1
- **Recipient organization:** VA EASTERN COLORADO HEALTH CARE SYSTEM
- **Principal Investigator:** Daniel James Reis
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2023-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10700406

## Citation

> US National Institutes of Health, RePORTER application 10700406, Enhancing Precision Sleep Medicine in traumatic Brain Injury: Examining the feasibility of Home-Based Measurement of Circadian Timing (1I21RX004414-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10700406. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*