The Feasibility of Home-Based Measurement of Circadian Timing for Veterans With TBI and Insomnia

NCT05665764 | Completed Results

• 1 other identifier: D4414-P
• Study Type: observational
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

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 after-effects such as depression, chronic pain, and fatigue. Current research suggests that TBI can impact numerous systems involved in sleep, suggesting that insomnia can have various causes and that a "one-size-fits-all" approach to treatment is likely inadequate. As such, it is necessary to determine which Veterans may benefit from standard evidence-based treatments, such as Cognitive Behavior Therapy for Insomnia, and which 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 disruptions of key circadian rhythms involved in sleep regulation (e.g., melatonin production), as well as the onset 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 actigraphy data) in Veterans with TBI and insomnia; and Aim 2) examine associations between circadian misalignment (i.e., the difference in timing between DLMO and attempted sleep onset), sleep disturbance, and functional impairment. Veterans with TBI and insomnia will be asked to wear a wrist-based actigraphy device for one week, which will collect data on light exposure and sleep-wake states. They will then be asked to self-collect seven hourly saliva samples under dim light conditions in their own home and mail them to a testing facility using a provided pre-paid shipping label. Saliva samples will be used to directly measure DLMO and actigraphy data will be used to indirectly estimate DLMO using established mathematical models of the human circadian pacemaker. Evaluating the feasibility of home DLMO measurement is a crucial first step for enhancing precision sleep medicine for Veterans with TBI and insomnia. Findings will inform the development and testing of tailored sleep interventions for use with this patient population.

Conditions

Brain Injuries, Traumatic; Sleep Initiation and Maintenance Disorders

Keywords

Circadian phase; Veteran; Traumatic Brain Injury; Insomnia

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adequate Data for Estimation of Dim Light Melatonin Onset (Self-Collected Saliva)

  This outcome will be considered feasible if 70% participants provide adequate data for measurement of dim light melatonin onset (DLMO). DLMO will be estimated via the observed salivary melatonin levels using a variable threshold method, defined as the time of day when melatonin rises above the mean of the individual's first three saliva samples plus two standard deviations of those first three samples. Additionally, adequate data will entail: 1) collection and return of at least 5 saliva samples; 2) \<5 minutes discrepancy between the reported and pre-specified collection times for the two saliva samples ultimately used to estimate DLMO; and 3) 50 lux of light exposure within 30 minutes of the two saliva samples ultimately used to establish DLMO. Each individual who meets these criteria will be considered a successful estimation of salivary-based DLMO.

  One week

• Number of Participants With Adequate Data for Estimation of Dim Light Melatonin Onset (Actigraphy)

  Dim light melatonin onset (DLMO) will be estimated using observed light exposure and sleep data via the extended Kronauer limit-cycle model of the human circadian pacemaker. This outcome will be considered feasible if 70% participants provide adequate actigraphy data. Adequate data will entail wearing the actigraphy device for at least 2 continuous days, with no interval of missing data (e.g., from covering the light sensor) during that time greater than 2 consecutive hours. Each Veteran who meets these criteria will be considered a successful estimation of actigraphy-based DLMO.

  One week

Secondary Outcomes (2)

• Functional Impairment (WHODAS 2.0 Summary Score)

  From baseline up to 1 week

• Sleep Disturbance (PROMIS Sleep Disturbance Total Score)

  From baseline up to 1 week

Other Outcomes (2)

• Circadian Misalignment (Salivary Dim Light Melatonin Onset)

  One week

• Circadian Misalignment (Actigraphy Dim Light Melatonin Onset)

  One week

Study Arms (2)

Veterans

Veterans will be the primary cohort for this study. Veterans who will be enrolled with have current insomnia and a history of traumatic brain injury.

Caregivers

Caregivers of enrolled veterans will be an optional cohort for this study. If applicable and willing to participate, caregivers of enrolled Veterans will be asked to provide collateral information regarding the Veteran's experience with the study.

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Potential participants will be all willing and eligible U.S. military Veterans aged 18-64 from the following populations: 1) those seeking outpatient services at the Rocky Mountain Regional Veterans Affairs (VA) Medical Center; and 2) those in existing clinical and research databases (e.g., the Rocky Mountain Mental Illness Research, Education and Clinical Center \[RM MIRECC\] research database).

You may qualify if:

• Veterans
• History of traumatic brain injury
• Current insomnia

You may not qualify if:

• Alcohol or substance abuse in the past 12 months
• History of psychotic or bipolar disorders
• Currently using of beta-blockers or melatonin-related substances (including over-the-counter or herbal products)
• Currently participating in a sleep-targeted psychotherapy
• Transmeridian travel (i.e., change in at least 2 time zones) in the past month
• Shift work (i.e., at least 6 hours between 10 pm and 8 am) in the past 6 months
• Currently pregnant or lactating
• Current untreated sleep apnea
• Lack of access to a home freezer
• Blindness
• Inability to independently provide informed consent

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Rocky Mountain Regional VA Medical Center, Aurora, CO

Aurora, Colorado, 80045-7211, United States

Location

Related Publications (1)

• Reis DJ, Armstrong AE, Miller C, Postolache TT, Forster JE, Brenner LA, Bahraini NH. The Feasibility of Home-Based Estimation of Circadian Timing in Veterans With Insomnia and Past Traumatic Brain Injury. J Head Trauma Rehabil. 2026 Apr 14. doi: 10.1097/HTR.0000000000001170. Online ahead of print.

  PMID: 41975564 DERIVED

Biospecimen

Retention: NONE RETAINED

No biospecimens will be retained. Saliva samples will be collected and tested for dim light melatonin onset as part of the study, after which they will be destroyed.

MeSH Terms

Conditions

Brain Injuries, Traumatic; Sleep Initiation and Maintenance Disorders

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Mental Disorders

Results Point of Contact

• Title: Daniel Reis
• Organization: Rocky Mountain VA MIRECC

daniel.reis2@va.gov

720-537-6080

Study Officials

• Daniel J Reis, PhD

  Rocky Mountain Regional VA Medical Center, Aurora, CO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2022
• First Posted: December 27, 2022
• Study Start: July 1, 2023
• Primary Completion: July 30, 2025
• Study Completion: December 31, 2025
• Last Updated: April 30, 2026
• Results First Posted: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Data used for publications may be made available until data are destroyed per institutional requirements.
• Access Criteria: Data will be made available for the validation of published findings or to support exploration of novel hypotheses. Requests to use data will be subject to a formal approval process. If approved, the requestor will be required to complete a data use agreement.

Locations

US (1)