Behavioral treatment of insomnia in active-duty service members with traumatic brain injury: study protocol for a randomized clinical trial

Abstract

Background

Traumatic brain injury (TBI) in the U.S. military can result in lasting health issues, with insomnia being a common symptom that worsens recovery, cognitive function, and performance, especially when combined with common co-occurring conditions like chronic pain, post-traumatic stress disorder (PTSD), and depression. Insomnia may be an important intervention target for managing post-concussive symptoms and overall functioning in service members who have sustained a TBI. However, the standard of care for the treatment of insomnia, Cognitive Behavioral Therapy for Insomnia (CBTI), is not widely available in military health care settings. The aim of this paper is to describe the design and analysis plan of the clinical trial to evaluate and compare two methods for delivering CBTI including in-person CBTI or CBTI delivered remotely via a clinician-supervised digital platform in a sample of active-duty service members presenting for care in a military TBI specialty clinic.

Methods

This is a phase II, randomized clinical trial designed to evaluate and compare the effects of CBTI (in-person or via a digital health platform) on sleep, behavioral health, and cognitive functions relative to treatment as usual among a sample of service members with a history of TBI. The effectiveness of in-person CBTI and CBTI delivered via a digital health platform, relative to treatment as usual, will be compared at baseline, after the six-week intervention, and again three months later on symptoms of insomnia, sleep quality, post-concussive symptoms, neurocognitive functioning, and psychological health.

Discussion

TBI is common in military personnel, often leading to insomnia that affects health and performance. While CBTI is the first-line recommended treatment for insomnia, CBTI is rarely implemented as the standard of care in military TBI specialty clinics, highlighting the need to assess its role in treating post-concussion symptoms and related issues. Clinical trials evaluating insomnia treatment in U.S. military service members with a history of TBI are essential to inform clinical practice for military TBI patients affected by insomnia and to potentially improve recovery, duty readiness, and cognitive function in this population.

Trial registration

ClinicalTrials.gov: NCT06867666. Registered on 2/26/2025.

Administrative information

Note: the numbers in curly brackets in this protocol refer to SPIRIT checklist item numbers. The order of the items has been modified to group similar items (see http://www.equator-network.org/reporting-guidelines/spirit-2013-statement-defining-standard-protocol-items-for-clinical-trials/).

Title {1}	Behavioral Treatment of Insomnia in Active-Duty Service Members with Traumatic Brain Injury: Study Protocol for a Randomized Clinical Trial
Trial registration {2a and 2b}	ClinicalTrials.gov: NCT06867666
Protocol version {3}	Date: 07 July 2025 Version: v1.11
Funding {4}	The trial is funded by the Congressionally Directed Medical Research Program (CDMRP).
Author details {5a}	Anne Germain, PhD, NOCTEM Health Inc Megan Wolfson, LCSW, NOCTEM Health Inc Emmanuel Espejo, PhD, Naval Health Research Center, Leidos, Inc. Anice Byrd, BA, Naval Health Research Center, Leidos, Inc. Sarah Jurick, PhD, Naval Health Research Center Lars Hungerford, PhD, General Dynamics Information Technology (GDIT) Support to Traumatic Brain Injury Center of Excellence Research Support Division, Research and Engineering Directorate Defense Health Agency, Naval Medical Center San Diego (NMCSD) Traci Sitzer, PhD, Naval Medical Center San Diego (NMCSD) LCDR Kevin Healy, DPT, OCS, WCC, Assistant Professor USUHS School of Medicine, Physical Medicine and Rehabilitation, Navy Medicine Readiness and Training Command San Diego Evan Chinoy, PhD, Naval Health Research Center Pinata Sessoms, PhD, Naval Health Research Center Meredith L. Wallace, PhD, Department of Psychiatry, University of Pittsburgh School of Medicine Andrew MacGregor, PhD, Naval Health Research Center
Name and contact information for the trial sponsor {5b}	Anne Germain, PhD Email: anne@noctemhealth.com Telephone: 412-212-3077
Role of sponsor {5c}	Employees of NOCTEM, LLC conceptualized the study design and/or statistical plan. NOCTEM, LLC will have no interaction with study participants, and statistical analysis will be conducted by an independent biostatistician. All publications will be reviewed by site investigators prior to submission.

Introduction

Background and rationale {6a}

Traumatic brain injury (TBI) is a public health concern in the U.S. military [1] and can result in long-term negative health sequelae [2, 3], increased healthcare costs [4, 5], and reduced operational readiness and performance [4, 6]. Sleep problems, including insomnia, are some of the most prevailing and persistent symptoms following TBI [2, 7].

Insomnia can adversely affect cognitive functioning and performance in key military occupations [8], and slow the overall recovery process following a TBI [9]. Both TBI and insomnia share certain comorbidities, such as chronic pain and psychological health conditions (e.g., post-traumatic stress disorder [PTSD] and depression) [7, 10], which can further degrade quality of life [11, 12].

Insomnia may be an important intervention target for managing post-concussive symptoms and overall functioning in service members who have sustained a TBI. In a study conducted by Barr and colleagues [13], a sample of seventy recently deployed service members with TBI, most of whom had been diagnosed with insomnia and/or obstructive sleep apnea, underwent three months of care to address sleep disruption (i.e., continuous positive airway pressure therapy, medications, and/or cognitive behavioral therapy (CBT)). Compared to those who did not experience improved sleep, those who endorsed more restorative sleep following the provision of care reported a reduction in PTSD and depression symptoms as well as a reduction in role limitation due to physical health. They also reported improved physical functioning, emotional well-being, social functioning, energy, and general health perceptions. A few feasibility studies and one recent study by Malarkey and colleagues [14] suggest that cognitive behavioral therapy for insomnia (CBTI) delivered in person or internet-guided is acceptable, feasible, and associated with short- and long-term improvements in sleep and fatigue among adults with a TBI history. In all these studies, CBTI led to greater improvement in insomnia severity or sleep quality compared to the control condition. There was also evidence that CBTI had positive effects on fatigue, daytime sleepiness, depression, PTSD, and general mental symptoms, but the findings were not consistent across all five studies [14–18]. Effects on cognitive functioning and post-concussive symptoms were examined in two of these studies, one with moderate to large positive effects [15], the other finding no significant association between improvements in insomnia and migraine-related disability [14]. While CBTI has been identified as the first-line recommended treatment for chronic insomnia by the VA/DoD Clinical Practice Guideline and other professional organizations [19–21], the implementation of CBTI in real-world practice settings, including those that serve active-duty personnel, is often rife with barriers. For example, a recent study conducted by Germain and colleagues [22], which included a survey and subsequent interviews with sleep healthcare providers in military treatment facilities and embedded clinical settings, highlighted two potential implementation barriers including: (1) the insufficient number of CBTI-trained providers to meet the demands and needs of active-duty service members and (2) the rigid and resource-intensive CBTI in-person delivery formats do not easily integrate into typical clinical workflows and active-duty service member occupational requirements.

Extant literature on CBTI with active-duty service members demonstrates that CBTI can be successfully used in military health settings [23–25] whether delivered in an in-person or digital format via an internet-guided approach (eCBTI). While eCBTI may help to overcome CBTI implementation barriers and increase treatment availability and accessibility, CBTI can be difficult to administer without the assistance of a therapist, especially in active-duty samples with TBI history, due to the complex nature of the treatment [23]. Indeed, eCBTI interventions are consistently less effective than in-person CBTI, and eCBTI demonstrated only moderate feasibility in the first study with TBI samples that included service members [14]. A clinician-supervised digital platform may be a more effective method for delivering CBTI remotely, offering the benefits of a digital treatment while simultaneously providing the support of a therapist to personalize the treatment and to assist patients with overcoming barriers to implementing the treatment procedures. As such, the aim of this paper is to describe the design and analysis plan of the clinical trial to evaluate and compare the effectiveness of CBTI delivered in-person or remotely via a clinician-supervised digital platform in a sample of active-duty service members presenting for care in a military TBI specialty clinic.

Objectives {7}

The objective of this study is to evaluate the impact of CBTI in a sample of active-duty service members with a history of TBI. Specifically, we will compare the effectiveness of traditional in-person CBTI and CBTI delivered via a clinician-supervised digital health platform, Clinician Operated Assistive Sleep Technology (COAST), relative to treatment as usual on symptoms of insomnia, post-concussive symptoms, neurocognitive functioning, and psychological health, including symptoms of PTSD, depression, and anxiety. We hypothesize that for all symptom domains of interest: (1) traditional in-person CBTI and CBTI with COAST will yield greater improvements than treatment as usual post-treatment and at the 3-month follow-up, and (2) in-person CBTI will be more effective than CBTI with COAST post-treatment and at the 3-month follow-up.

Trial design {8}

This is a phase II, randomized clinical trial designed to evaluate and compare the effects of CBTI (in-person or via a digital health platform) on sleep, behavioral health, and cognitive functions relative to treatment as usual among a sample of service members with a history of TBI. Participants will be randomized to one of three conditions including in-person CBTI, CBTI via COAST, or treatment as usual. For the two active CBTI groups, measures of insomnia, sleep quality, post-concussive symptoms, neurocognitive functioning, and psychological health will be completed at baseline before the study treatments are delivered, immediately after the six-week intervention, and again three months later. In the treatment as usual condition, participants will not receive any of the two study sleep interventions but may attend the usual sleep classes offered through the clinical study site’s TBI Clinic. They will also complete the baseline assessment and then be reassessed after the six-week intervention and again three months later.

Methods: participants, interventions, and outcomes

Study setting {9}

The study will be conducted at the Naval Health Research Center and Naval Medical Center San Diego (NMCSD) TBI Clinic in San Diego, California.

Eligibility criteria {10}

Eligibility criteria were selected to optimize the generalizability of the anticipated findings and their impact on active-duty service members with a history of TBI and who suffer from chronic insomnia. Eligible participants include active-duty service members, primarily U.S. Navy Sailors and activated reservists, who present to the TBI Clinic at NMCSD with symptoms of chronic insomnia (Pittsburgh Sleep Quality Index score ≥ 9) [26], a history of TBI, own a smart device and, if applicable, are stable for at least 8 weeks on psychotropic and hypnotic medications and are stable on continuous positive airway pressure therapy (CPAP) for sleep apnea for at least 90 days and usage of four hours or more per night for at least 70% of the nights. Service members will not be eligible if they are unable to give informed consent, have a history of severe TBI, potential alcohol use disorder (Alcohol Use Disorders Identification Test-Consumption score ≥ 5) [27], suicidal risk meriting crisis intervention, inability to comprehend or read English, seizure disorder or a serious mental health condition (e.g., Bipolar disorder or psychosis), hypersomnia disorder, or do shift work (e.g., working rotating shifts or shifts requiring the individual to report to work earlier than 6 am). These exclusion criteria were established to minimize the risks associated with participation in the trial.

Study therapists providing in-person CBTI and CBTI via COAST will be credentialed doctoral-level clinicians with experience in behavioral sleep medicine.

Who will take informed consent? {26a}

TBI Clinic patients may be referred directly to the research coordinator by a TBI team member or self-referred by initiating contact with the research coordinator via telephone or email. During the potential participant’s initial contact with the research coordinator, a scripted description of the study will be provided and questions about the study addressed. For potential participants who remain interested in participating in the trial after receiving information about the study and obtaining answers to questions that may have arisen, oral consent will be obtained to conduct a brief telephone screening interview to assess eligibility and safety for trial participation, including the presence of sleep complaints consistent with insomnia, current medications, and recent hospitalization. Willingness to participate and eligibility will then be confirmed and informed consent for trial participation will be obtained at the consent appointment with the research coordinator.

Additional consent provisions for collection and use of participant data and biological specimens {26b}

In addition to consent for trial participation, participants will be asked to optionally provide consent for the following: (1) audio recordings and their transcriptions of in-person CBTI sessions (for participants assigned to the in-person CBTI treatment group) to be used to confirm study therapist adherence to the protocol and/or to be stored for future research, and (2) de-identified data to be kept for use in future research studies by study investigators.

Interventions

Explanation for the choice of comparators {6b}

CBTI is the treatment of choice for the management of chronic insomnia as recommended by the American Academy of Sleep Medicine, American College of Physicians, and the VA/DoD [19–21]. CBTI demonstrates clinically significant remission and responder rates across studies and durable long-term treatment gains [20]. Though CBTI is generally effective across delivery methods, non-traditional delivery of CBTI (e.g., via internet, video, or self-help delivery) has performed less favorably than traditional CBTI, including in a comparative effectiveness study with active-duty service members [23]. However, as CBTI is not typically offered as part of the first line of care in military TBI specialty clinics, digital CBTI may reduce the burden of CBTI for healthcare providers in this setting and allow providers to expand service member access to insomnia treatment. It is also possible that for patients with a TBI history who may present with difficulty remembering or other cognitive symptoms, digital delivery of CBTI may offer some benefits due to using the patients’ mobile smart device to automate reminders and make treatment information easily accessible. Therefore, we selected two CBTI delivery methods for this trial, in-person and digital via a clinician-supervised platform called COAST. A clinician-supervised digital method was selected because CBTI can be difficult to administer without the assistance of a therapist, especially in active-duty samples with TBI, due to the complex nature of the treatment [23]. Both CBTI delivery methods will be compared to treatment as usual among a sample of service members with TBI.

Intervention description {11a}

In-person CBTI and CBTI via the clinician-supervised digital platform, COAST, will be delivered by credentialed doctoral-level clinicians with experience in behavioral sleep medicine. Treatment will be conducted individually every week for six weeks. Both treatment groups will be asked to use the COAST patient app to complete a daily sleep diary available for review by their study therapist on the COAST clinician web-based portal. In-person CBTI treatment will be delivered in-person at the TBI Clinic at NMCSD or at the Naval Health Research Center or via telehealth on a secure, HIPAA-compliant platform. The specific CBTI protocol to be used for in-person treatment is the same as that used in a prior randomized controlled trial of CBTI in active-duty service members with insomnia [23]. CBTI via COAST will be delivered by a study therapist with weekly treatment recommendations selected by the study therapist and delivered remotely via the COAST patient app. Participant progress will be monitored via the COAST clinician web-based portal. The study therapist and participants in the COAST treatment group will communicate via the platform’s embedded HIPAA-compliant messaging system.

Criteria for discontinuing or modifying allocated interventions {11b}

Robust screening procedures to confirm prospective participant eligibility to participate in this trial are in place to ensure the clinical appropriateness of a course of CBTI for participants randomized to in-person or COAST-delivered CBTI. CBTI procedures and techniques involve no more than minimal risk and are the same as would be expected from the traditional in-person sleep intervention. Each participant’s study therapist will make determinations about any CBTI treatment modifications that may be required during the 6-week treatment course or if it is deemed that participation in CBTI should be terminated.

Strategies to improve adherence to interventions {11c}

No study-specific strategies are being used with the aim of enhancing participant adherence to CBTI. Study therapists offering in-person or COAST-delivered CBTI will utilize standard motivational strategies (e.g., psychoeducation on mechanisms underlying sleep regulation, best practices for daily adherence to a prescribed rise time) to support participant engagement with treatment. Participants in both CBTI treatments will use the COAST patient app to complete their daily sleep diary. Participants in the in-person CBTI treatment may find it easier to complete a digital sleep diary compared to a pen and paper diary commonly offered in traditional CBTI.

Relevant concomitant care permitted or prohibited during the trial {11d}

Participating in the trial will not interfere with concomitant care. Across all treatment conditions, participants will be encouraged to follow the recommendations of their treatment team at the TBI Clinic. These recommendations may include a sleep class, including information on healthy sleep practices.

Provisions for post-trial care {30}

The anticipated risk for participants is believed to be minimal. As part of their regular TBI care, service members with insomnia may be offered the same cognitive behavioral interventions for insomnia that are being used in the in-person CBTI and CBTI via COAST treatment arms. The procedures for assessment (survey, sleep diary), monitoring (weekly assessment of symptoms, side effects, and progress), and the recommendations for behavioral modifications to promote consolidated restorative sleep involve no more than minimal risk and align with those recommended by the American Academy of Sleep Medicine, American College of Physicians, and the VA/DoD Guidelines for the Management of Chronic Insomnia [19–21]. By request, participants randomized to in-person or COAST-delivered CBTI can receive a summary that they can then share with their treating provider.

Outcomes {12}

The primary outcome measures of interest include the Insomnia Severity Index, Rivermead Post-Concussion Questionnaire, Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5), Patient Health Questionnaire—8 items (PHQ-8), and Generalized Anxiety Disorder Screen—7 items (GAD-7).

The Insomnia Severity Index [28, 29] will be administered at every other weekly intervention session and at baseline, post-intervention, and the 3-month follow-up to measure insomnia symptom severity. The Insomnia Severity Index is a 7-item self-report questionnaire that assesses the subjective severity of insomnia symptoms, including noticeability of daytime impairments and concerns caused by sleep difficulties. Each item is rated on a 0–4-point scale. Scores from 0 to 7 reflect not clinically significant insomnia; scores from 8 to 14 reflect subthreshold insomnia; and scores from 15 to 28 reflect clinically significant insomnia. Treatment response is defined as a reduction of 6–8 points or more on this measure.

The Rivermead Post-Concussion Questionnaire [30, 31] will be administered at baseline, post-intervention, and the 3-month follow-up to examine post-concussive symptoms. It is a 16-item self-report questionnaire that assesses post-concussive symptoms in the physical, cognitive, and somatic domains. This measure has demonstrated good reliability and consistency and is recommended by the Department of Defense (DoD) and the Department of Veterans Affairs (VA) for TBI research and clinical evaluations.

The PCL-5 [32, 33] will be administered at baseline, post-intervention, and the 3-month follow-up. It is a self-report questionnaire that includes 20 items that correspond to the four symptom clusters of PTSD. Each item is rated on a 0–4 point scale. The sum of item scores ranges from 0 to 80, with higher scores indicating more severe PTSD symptoms. The PCL-5 is used extensively in clinical practice and research investigating PTSD in military populations.

The PHQ-8 [34] will be administered at baseline, post-intervention, and the 3-month follow-up. The 8 items are based on the Diagnostic and Statistical Manual IV (DSM-IV) diagnostic criteria for depression, with the item assessing the frequency of suicidal thoughts removed. Each item is scored from 0 to 3 with higher scores indicating more severe depression symptoms.

The GAD-7 [35, 36] will be administered at baseline, post-intervention, and the 3-month follow-up. This self-report measure is designed to assess the severity of symptoms consistent with generalized anxiety disorder based on DSM-IV diagnostic criteria. Each item is scored from 0 to 3 with higher scores indicating more severe anxiety symptoms.

The secondary outcome measures of interest include the COAST sleep diary, Brief Fatigue Inventory, and the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0).

The COAST sleep diary will be completed for one week at baseline, post-intervention, and the 3-month follow-up, as well as every day during the acute intervention phase to assess changes over time in sleep-wake patterns (e.g., sleep onset latency, sleep efficiency, sleep duration) and daytime behaviors that may compromise or facilitate sleep (e.g., naps, caffeine use, alcohol consumption). Participants will be prompted to self-report on sleep-related items upon awakening in the morning and to self-report on daytime behaviors in the evening and before bedtime.

The Brief Fatigue Inventory [37] will be administered at each weekly intervention session and at baseline, post-intervention, and the 3-month follow-up to assess fatigue levels and interference with functioning over the previous 24 hours. The nine items are rated from 0 to 10, with higher scores indicating higher levels of fatigue and greater interference. The measure has good psychometric properties and has demonstrated sensitivity to change in a pilot study of CBTI in TBI patients [16].

The WHODAS 2.0 [38, 39] will be administered at baseline, post-intervention, and the 3-month follow-up. It is a 12-item self-report questionnaire assessing general health and disability. Items are rated from “None,” “Mild,” “Moderate,” “Severe,” to “Extreme or cannot do,” indicating difficulty over the past month. The WHODAS 2.0 has excellent psychometric properties.

Exploratory neurocognitive performance outcome measures include the Test of Premorbid Function (TOPF), the Trail-Making Test (TMT), the Digit Span Test, the Symbol Digit Modalities Test (SDMT), and the Medical Symptom Validity Test (MSVT).

The TOPF will be administered to estimate premorbid intellectual functioning in adults [40]. During TOPF execution, the participant is given a list of 50 phonemically irregular words and asked to pronounce the words in consecutive order to the best of their ability, even if they think the pronunciation is incorrect. The TOPF has excellent internal consistency (0.90–0.97) and high test-retest reliability (0.90–0.94).

The TMT is a widely used measure of psychomotor speed and executive functioning [41]. The TMT is a paper-and-pencil test consisting of two trials, Part A and Part B. Part A requires the participant to draw a line connecting numbered circles in order and depends largely on the participant’s psychomotor speed and visual search abilities. Part B requires the participant to draw a line connecting circles with numbers or letters in alternating sequential-alphabetic order. Part B is believed to place additional demands on the participant’s working memory and cognitive flexibility. The score on both parts of the TMT is determined by the time required to complete each trial. The TMT has previously been shown to be impacted by changes in sleep [42].

The Digit Span Test, from The Wechsler Adult Intelligence Scale—Fourth Edition (WAIS-IV), will be administered to assess working memory [43]. The Digit Span Test consists of 3 subsets: Digit Span Forward, Digit Span Backward, and Digit Span Sequencing. Digit Span Forward has the participant repeat back numbers that are spoken to them (e.g., 6–3–8–2 is 6–3–8–2). Digit Span Backward has the participant repeat back numbers spoken to them in reverse order (e.g., 3–9–4 is 4–9–3). Digit Span Sequencing has participants order the numbers from lowest to highest (e.g., 8–2–6–4-1 is 1–2–4–6–8). The Digit Span Test displays excellent internal consistency (0.93) and good test-retest reliability (0.82).

The SDMT will be administered to measure visual attention and working memory, visual scanning, and processing speed [44]. SDMT instructs the participant to decode a series of symbols as quickly as possible by assigning the appropriate number to the symbol according to the provided key. The SDMT has been shown to be impacted by changes in sleep in prior research.

The MSVT will be administered as a validity metric that assesses verbal learning, verbal memory, and response consistency [45]. The MSVT is a computerized measure designed to determine whether effort is sufficient to produce valid results on neuropsychological tests. Participants scoring below the cutoff (i.e., below 85% on any of the three scales) will be excluded from analyses of neuropsychological assessments, as has been done in other studies of military and veteran populations with TBI [46, 47].

Participant timeline {13} (Fig. 1)

Fig. 1.

Schedule of enrollment, interventions, and assessments for study participants

Sample size {14}

To achieve study objectives, a sample of 168 service members, or 56 per group (in-person CBTI, CBTI via COAST, and treatment as usual), is sought. With 56 service members per group and an estimated 80% retention at post-treatment (44 service members per group), for comparing in-person and COAST delivered CBTI relative to treatment as usual on insomnia and post-concussive symptom severity, we will have 80% power to detect a medium Cohen’s d effect size of d = 0.53. For comparing in-person and COAST delivered CBTI relative to treatment as usual on psychological health symptoms (i.e., PTSD, depression, and anxiety), we will have 80% power to detect a medium Cohen’s d effect size of d = 0.62. Estimating a 60% retention for the 3-month follow-up, the sample size of 33 service members per treatment group will achieve 80% power to detect a medium effect size Cohen’s d = 0.60 to 0.70. Using the same estimated attrition rates, for comparing in-person CBTI relative to CBTI delivered via COAST, we expect 80% power to detect Cohen’s d effect sizes of d = 0.62 to 0.72. For the 3-month timepoint comparison, we expect 80% power to detect medium-to-large effect sizes of d = 0.70 to 0.81.

Recruitment {15}

A team of community-based research partners with expertise in working with patients with a history of TBI and/or military TBI specialty clinic operations has been identified for this trial. Feedback from this team guided the development of current recruitment and enrollment procedures to ensure these procedures are readily implementable in clinical contexts and minimize the research burden on participants and clinic resources. Additionally, we have built strong relationships with personnel from the NMCSD campus, including the TBI Clinic intake coordinator and clinicians, who will be working closely with our team to facilitate study referrals.

Assignment of interventions: allocation

Sequence generation {16a}

Study participants will be stratified on the basis of sex and by presence or absence of use of psychotropic medication or comorbidities (yes/no). Within each stratum, participants will be randomized in a 1:1:1 manner to in-person CBTI, CBTI via COAST, or treatment as usual. Randomization within each stratum will follow a permuted block design to ensure that the treatments are equally distributed across strata. The use of stratified randomization with permuted block randomization will provide a balance of treatment arms across medication use. The randomization schedule will be completed using a random number generator with randomly permuted blocks.

Concealment mechanism {16b}

The randomization schedule will be accessed by the research coordinator only at the time of allocation to one of the three treatment arms.

Implementation {16c}

After obtaining informed consent for the study, the participants will undergo a baseline interview assessment to determine whether they meet all inclusion criteria or any of the exclusion criteria. If the participant meets all study criteria, they will proceed with the completion of the baseline questionnaires and brief neuropsychological assessments. All participants will also receive instructions on how to download and use the COAST app and will be instructed to use the app to complete the daily sleep diary for one week. Once the participant has demonstrated good adherence to completing sleep diary assessments (i.e., at least 5 out of 7 days of sleep diary assessments), they will be randomized to in-person CBTI, CBTI via COAST, or treatment as usual. Participants randomized to in-person CBTI will be scheduled for their first in-person appointment ideally within one week. Participants randomized to COAST will be introduced by the research coordinator to the COAST study therapist and will initiate CBTI via COAST under their close supervision. Participants randomized to treatment as usual will be scheduled to again meet with the research coordinator in six weeks to repeat the baseline questionnaires and neuropsychological assessments.

Assignment of interventions: blinding

Who will be blinded {17a}

Blinding of participants or study therapists is not possible in this trial. However, the biostatistician who performs the analyses will remain masked to the randomization assignment to reduce bias.

Procedure for unblinding if needed {17b}

Not applicable: neither participants nor study therapists will be blinded in this trial.

Data collection and management

Plans for assessment and collection of outcomes {18a}

Data for primary and secondary outcomes will be collected via the COAST patient app. The app is designed with validation checks for data completeness and input parameters to ensure data quality. Exploratory neurocognitive performance outcome measures will be collected during in-person appointments by the research coordinator. Prior to administering the assessments, the research coordinator will have completed training with a licensed neuropsychologist to ensure that all measures are being administered following the standardized procedures. Details on the outcome measures for this trial are in the section titled Outcomes.

Plans to promote participant retention and complete follow-up {18b}

To support participant retention throughout the intervention period and follow-up timepoints, participants can be compensated up to $150 in gift cards for completion of the post-intervention and 3-month follow-up assessments.

Data management {19}

During the intervention phase, post-treatment, and at the 3-month follow-up, data will be collected securely, electronically, and prospectively via Qualtrics and the COAST app. The database storing data collected via the COAST app is housed in a secure cloud behind a firewall. For participants randomized to in-person CBTI and who consent for audio recordings, these recordings will be stored on a secured, password-protected non-networked laptop computer located in a locked cabinet within a locked room. Audio files will be deleted from the actual audio recorders as soon as the files are transferred. If the participant consented to have these audio files used for possible future research, the files will remain securely stored. If the participant consented to recordings only for confirmation of therapist adherence to the study protocol, files will be deleted at study completion. For neuropsychological assessments not administered via the COAST app, data will be entered into a secure electronic database by the research coordinator under the participant’s research identification number. All electronic study data will be de-identified, and accessible only by study personnel.

Confidentiality {27}

All participants will have a unique identifier number that will be used on forms and for data storage purposes. Participant name and contact information collected and used by the research coordinator for the purpose of scheduling in-person baseline and follow-up visits will be maintained separately in a password protected document separate from any data form or files and destroyed at study completion.

Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}

Not applicable; no biological specimens are being collected for this trial.

Statistical methods

Statistical methods for primary and secondary outcomes {20a}

Prior to hypothesis testing, data will be explored using descriptive summary statistics. At baseline, post-treatment, and at follow-up, descriptive statistics will be presented for the entire sample and stratified by treatment randomization and other key features (e.g., current use of psychotropic medications, comorbid conditions, or sex). If needed, we will transform outcomes to address any asymmetry. We will assess the balance of key covariates (e.g., age, sex, race, rank, years of service, chronicity of TBI) between treatment groups graphically and with standardized effect sizes, assisting us in evaluating the distribution of data and determining if assumptions are met for subsequent modeling approaches. We expect these variables to be similar in the three treatment arms due to randomization. To test Hypothesis 1, in-person CBTI and CBTI via COAST will yield greater improvements across all three outcome domains of interest (i.e., sleep, behavioral health, and cognitive functions) compared to treatment as usual, we will use Linear Mixed Effects Models (LMEs) to regress each outcome (measured at baseline, post-treatment, and at the 3-month follow-up) on categorical time (baseline, post-treatment, 3-month follow-up), group (CBTI, CBTI via COAST, treatment as usual), the group by time interaction, and covariates, with planned pairwise comparisons used to test a priori hypotheses regarding group differences within and across timepoints. For hypothesis testing, two-sided Wald t-test or Wald F-tests from these general linear models will be used. To test Hypothesis 2, we will use an additional planned pairwise comparison in the models fit to compare in-person CBTI vs. CBTI via COAST.

Interim analyses {21b}

Not applicable; study procedures involve no more than minimal risk. There are no plans for interim analyses to potentially revise trial procedures or prematurely end the trial.

Methods for additional analyses (e.g., subgroup analyses) {20b}

Not applicable; analyses will focus on hypothesis at baseline, post intervention, and the 3-month follow-up. Subgroup analyses may be conducted if the qualitative review of the sample data suggests that subsamples of patients may have differing patterns of response to treatment based on the three outcome domains of interest, or if the relationship among the domains of interest appears to differ with demographic, clinical, and military characteristics.

Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}

The proposed linear mixed-effects will produce consistent estimations of the regression parameters under the missing at random, missing completely at random mechanisms, or with covariate-dependent missing data mechanisms after accounting for relevant covariates in the models. We will further protect against potential biases introduced by missing outcome and covariate data through a combination of multiple imputations with intent-to-treat analyses. If there is evidence of covariate-dependent missing data, we will include any covariates related to missingness in the models. If there is evidence of data missing not at random, we will also stratify the participants into subgroups that share the same missing data pattern and estimate the statistical model separately for each missing data pattern; these patterns can then be averaged using pattern mixture models.

Plans to give access to the full protocol, participant level-data, and statistical code {31c}

Coded data from this study will be submitted to the Federal Interagency Traumatic Brain Injury Research (FITBIR) Informatics System, a computer system run by the National Institutes of Health that allows for easier exchange of data for researchers studying TBI. Deidentified data will be sent to FITBIR during and after the study. More information about FITBIR can be found at: https://fitbir.nih.gov.

Oversight and monitoring

Composition of the coordinating centre and trial steering committee {5d}

Bi-monthly team meetings will be held with the principal and site investigators, coordinator, study therapists, community-based research partners, and other collaborators to discuss trial activities and timelines and to verify conduct is in alignment with the study protocol. Specifically, meetings will review the progress of the research study, outcome and adverse event data to closely monitor the anticipated risk/benefit ratio and determine whether any changes are necessary, assessment of any external factors or relevant information that may impact the trial, and review of study procedures designed to protect the privacy of research participants and the confidentiality of their research data.

Composition of the data monitoring committee, its role and reporting structure {21a}

We have assembled a team of experts who will convene at least bi-annually to review data validity and integrity. Members of the team include those with expertise in biostatistics, sleep medicine, TBI, clinical trial methods, and dissemination and implementation of evidence-based practices. Items for review during scheduled meetings may include protocol and protocol revisions, participant flow and retention, safety data including occurrence of side effects and unanticipated or serious adverse events, and magnitude of improvements in treatment arms.

Adverse event reporting and harms {22}

Principal and site investigators will be informed of adverse events and follow IRB guidelines for reporting these events. Should any new information arise that alters the risk/benefit ratio of participating in the study, this information will be swiftly communicated to current and prospective participants.

Frequency and plans for auditing trial conduct {23}

Investigators and research staff will include as part of their bi-monthly team meetings a review of trial conduct including participant recruitment, enrollment, and retention, data quality, changes to the risk/benefit ratio of study participation, and procedures for data privacy and participant confidentiality.

Plans for communicating important protocol amendments to relevant parties (e.g., trial participants, ethical committees) {25}

All protocol amendments will be completed in accordance with current IRB guidelines. Should an amendment be made that directly affects study participants, they will be promptly informed of these changes by the research coordinator.

Dissemination plans {31a}

Findings from this trial will be submitted for peer-reviewed publication as well as for presentation at scientific conferences. A final report will also be submitted to the study sponsor (CDMRP). We also anticipate creating a brief report on lessons learned and recommendations for the implementation of digital CBTI to augment capabilities in behavioral sleep medicine at the TBI point of care for distribution to healthcare providers and other relevant stakeholders within the Department of Defense/Defense Health Agency.

Discussion

TBI is widespread among military personnel, and un-treated or under-treated symptoms can create performance decrements. Sleep problems, such as insomnia, are common after TBI and present a risk to the overall health and readiness of military service members. It is thus essential to examine the effectiveness of clinical treatments for insomnia following TBI among service members, not only to improve sleep, but potentially to (1) improve other co-occurring symptoms (i.e., chronic pain, depression, and PTSD), (2) facilitate a more expedient return to full duty status, and (3) perform occupational duties at an optimal level. While many military treatment facilities have established TBI clinics, CBTI, the recommended treatment for insomnia, is an infrequent offering for military TBI programs. Increasing the availability of insomnia treatment in service members with a TBI history may directly support the readiness of the warfighter and lead to an overall healthier warfighting force. This clinical trial is designed to assess whether insomnia is an important intervention target for managing post-concussion symptoms, psychological and cognitive sequelae, and overall functioning in active-duty service members who have sustained a TBI and methods for delivering insomnia care (in-person versus clinician-supervised digital CBTI) for this population. In the short term, the study will provide new insights and guidance on the impact of CBTI on insomnia comorbid with TBI and inform and support clinical practice for military TBI patients affected by insomnia and the clinicians who treat them.

Trial status

This study received ethics approval from the Naval Health Research Center’s Institutional Review Board on 30 January 2025 and from the Office of Human Research Oversight (OHRO) (Log E05743.1a). Recruitment is anticipated to begin on August 1, 2025, and is expected to be completed by March 2027.

Abbreviations

CBTI

Cognitive Behavioral Treatment for Insomnia

COAST

Clinician Operated Assistive Sleep Technology

CPAP

Continuous Positive Airway Pressure

DoD

Department of Defense

DSM-IV

Diagnostic and Statistical Manual IV

eCBTI

Internet-guided Cognitive Behavioral Treatment for Insomnia

GAD-7

Generalized Anxiety Disorder Screen—7 items

MSVT

Medical Symptom Validity Test

NMCSD

Naval Medical Center San Diego

PCL-5

Post-Traumatic Stress Disorder Checklist for DSM-5

PHQ-8

Patient Health Questionnaire—8 items

PTSD

Post-Traumatic Stress Disorder

SDMT

Symbol Digit Modalities Test

TBI

Traumatic Brain Injury

TMT

Trail-Making Test

TOPF

Test of Premorbid Function

U.S.

United States

VA

Veterans Affairs

WHODAS 2.0

World Health Organization Disability Assessment Schedule 2.0

Authors’ contributions {31b}

AG, AM, and LH conceived the study and led the proposal and protocol development. AG, MLW, AM, PS, and EE designed the study and developed the proposal. LH, TS, SP provided input as community-based partners for the study measures and design. AB and MW developed the study standards of operations as per the protocol. MW and AG drafted the initial version of the manuscript. All listed authors offered meaningful contributions to the final version of this manuscript. All authors read and approved the final manuscript. The opinions and assertions contained herein are those of the authors and do not necessarily reflect the views of the US Army, US Navy, US Air Force, or the US Department of Defense. The views and opinions expressed herein should not be construed as an official position, policy, or decision of the US Army, US Navy, US Air Force, or the US Department of Defense unless so designated by other documentation. No official endorsement should be made Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise, does not necessarily constitute or imply its endorsement, recommendation, or favoring by the US Government. I am a military service member of the U.S. Government. This work was prepared as part of my official duties. Title 17, U.S.C. §105 provides that copyright protection under this title is not available for any work of the U.S. Government. Title 17, U.S.C. §101 defines a U.S. Government work as work prepared by a military service member or employee of the U.S. Government as part of that person’s official duties. This work was supported by Congressionally Directed Medical Research Programs under work unit no. 62403. The views expressed in this work are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government. The study protocol was approved by the Naval Health Research Center Institutional Review Board (protocol number NHRC.2024.0014) in compliance with all applicable federal regulations governing the protection of human subjects.

Funding {4}

This trial is sponsored by Congressionally Directed Medical Research Programs (CDMRP; Award HT9425-24-1-0667).

Data availability {29}

NOCTEM and researchers at Naval Health Research Center (NHRC) will have access to the final trial dataset. A Collaborative Research and Development Agreement (CRADA) is in place between NOCTEM and NHRC.

Declarations

Ethics approval and consent to participate {24}

This study received ethics review and approval from Naval Health Research Center’s Institutional Review Board on 30 January 2025 and from the Office of Human Research Oversight (OHRO) (Log E05743.1a). Informed consent to participate will be obtained from all participants.

Consent for publication {32}

Not applicable.

Competing interests {28}

NOCTEM Health, Inc. owns all interests of NOCTEM, LLC. Dr. Germain is the Founder and CEO of NOCTEM Health Inc, LLC. Ms. Wolfson is employed by NOCTEM Health, Inc. Both Dr. Germain and Ms. Wolfson own stocks in NOCTEM Health.