Targeted Multidomain (T-MD) Interventions for Complex Mild Traumatic Brain Injury (mTBI)

NCT ID: NCT04549532

Last Updated: 2025-10-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 169 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-15
• Study Completion Date: 2025-04-09

Brief Summary

Objective: This 3-year multisite RCT will determine the effectiveness of a targeted multidomain intervention (T-MD) (anxiety/mood, cognitive, migraine, ocular, vestibular; and sleep, autonomic) compared to usual care (behavioral management) in military-aged civilians with complex mTBI.

Detailed Description

A prospective single-blinded two-group multicenter randomized controlled trial (RCT) of a targeted multi-domain intervention in military-aged civilians with complex mTBI will be conducted at the University of Pittsburgh Medical Center Sports Concussion Program (UPitt) and Inova Sports Concussion Clinic. During year 1 the investigators will obtain appropriate contract and research agreements, and institutional, site-specific, and Human Research Protection Official (HRPO) Institutional Review Board (IRB) approvals for the trial. This study will enroll 250 military-aged civilians with a diagnosed complex mTBI from UPitt (125) and Inova (125). Upon enrollment, participants will complete a comprehensive multidomain evaluation of symptoms and impairment that will inform an adjudication process to determine affected clinical profiles and targeted interventions. Participants will then be randomized to either the T-MD or usual care intervention arm. The T-MD group will receive targeted interventions (cognitive behavioral therapy, cognitive accommodations/activities, behavioral regulation for headache/migraine, oculomotor exercises, behavioral sleep intervention, vestibular rehabilitation, graded exertion) for affected clinical profiles based on the adjudication process, whereas usual care will only receive behavioral management strategies (e.g., sleep, nutrition, hydration, activity, stress management). In-clinic treatment sessions will be complemented with at-home activities and compliance will be monitored using a text-based tool. Data collection will include demographic data, medical history, health care utilization (the number of visits and utilization costs), and length of time to return to activity (RTA). Primary outcomes for Aim 1 will be assessed at baseline, 2-week, 4-week, and 3-month post-intervention intervals. Secondary outcomes for Aim 1 will be assessed at baseline, 2-week, and 4-week post-intervention intervals, with select outcomes being measured again at 3-months. The investigators will also determine if participants are recovered (i.e., medically cleared for full return to activity) at 2 weeks, 4 weeks and 3 months post-intervention. Additionally, the investigators will tabulate each participant's healthcare utilization and related costs using electronic health record (EHR) at the conclusion of participation in the study protocol. For Aims 2 and 3, in years 2-3, concurrent measures of brain activation will be obtained (i.e., CBF) in the cerebral cortex using fNIRS for all participants at enrollment and 4 weeks-post intervention. Primary outcome measures for Aims 2 and 3 will be oxygenated (activation) and deoxygenated (deactivation) hemoglobin in regions of interest in the cerebral cortex at rest. Secondary outcomes will include the same fNIRS measures during cognitive and exertion activities. We will control for the time since injury in all analyses. For Aim 1, a linear mixed model will be used to compare primary and secondary outcomes between groups, while accounting for covariates. For Aim 2, a linear mixed model will be used to compare brain regions of interest, while accounting for covariates. For Aim 3, bivariate and partial correlational analyses will be conducted.

Conditions

Concussion, Mild

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

T-MD Intervention Group

Participants will be prescribed 1+ interventions tailored to affected domains.Anxiety/Mood-Cog beh therapy(CBT) for maladaptive beliefs/avoidance/coping behaviors. Graded exposure/activity/relaxation exercises, cognitive restructuring. Cognitive-Accommodations for reduced work/school time/delayed deadlines, more frequent/longer cognitive rest during symptom-provoking activities. Migraine/Headache: Education, relaxation training/mindfulness based therapy. Ocular-Exercises for ocular symptoms, near point convergence, may include Brock string, pencil push-ups, fixation, saccade tracking, pursuits. Sleep-Sleep regulation/hygiene. Mindfulness-based training, morning physical activity, CBT.Vestibular-Exercises for dizziness, visual motion sensitivity, gait, imbalance that may include gaze stability, visual habituation, static and dynamic balance/gait.Autonomic-Graded aerobic exercise. Perform daily aerobic exercise, goal 80% HR max on a stationary bike/treadmill/walking/jogging.

Group Type: EXPERIMENTAL

Targeted Multidomain

Intervention Type: BEHAVIORAL

Participants in the T-MD intervention group will be prescribed targeted interventions to address each individual's symptoms, impairments, and functional limitations in the areas of anxiety/mood, cognitive, migraine/headache, ocular, vestibular, sleep, autonomic. The length of the intervention period will be 4 weeks or until RTA, whichever comes first.

Behavioral Management

Participants in control group will receive standardized behavioral management strategies including: activity, hydration, nutrition, sleep, and stress management strategies. These strategies provide general methods to manage concussion symptoms and regulate daily activities to assist in the recovery of concussion. Clinicians will discuss and review a behavioral strategies handout with each participant and answer any questions they may have about the information in the handout. Contact time between clinicians and patients will be similar to avoid effects associated with more or less contact time.

Group Type: ACTIVE_COMPARATOR

Behavioral Management

Intervention Type: BEHAVIORAL

1.3. Usual Care (Controls) Group Participants randomized to the usual care (control) group will receive standardized (i.e., all participants in this group will receive the same interventions) behavioral management strategies that include activity, hydration, nutrition, sleep, and stress management strategies.

Interventions

Targeted Multidomain

Participants in the T-MD intervention group will be prescribed targeted interventions to address each individual's symptoms, impairments, and functional limitations in the areas of anxiety/mood, cognitive, migraine/headache, ocular, vestibular, sleep, autonomic. The length of the intervention period will be 4 weeks or until RTA, whichever comes first.

Intervention Type: BEHAVIORAL

Behavioral Management

1.3. Usual Care (Controls) Group Participants randomized to the usual care (control) group will receive standardized (i.e., all participants in this group will receive the same interventions) behavioral management strategies that include activity, hydration, nutrition, sleep, and stress management strategies.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• 18-49 years of age
• Normal/corrected vision
• Diagnosed with complex mTBI in the past 8 days-6 months with clear mechanism of injury
• Glascow coma scale (GCS) score no less than 13
• Reported or sign of mTBI including loss of consciousness, amnesia, disorientation/confusion, dizziness, imbalance, memory problems, vomiting
• Complex mTBI-related symptoms and/or impairments in at least one of the following areas: anxiety/mood, cognitive, migraine, ocular, vestibular, sleep, autonomic; per a comprehensive assessment, clinical exam/interview, and adjudication process.

Exclusion Criteria

• History of vestibular disorder (e.g., benign paroxysmal positional vertigo, unilateral, or bilateral vestibular hypofunction)
• History of neurological disorder
• Previous moderate to severe TBI
• History of brain surgery, malformations or tumors
• Diagnosed with cardiac, peripheral or cerebrovascular disease
• Experienced chest pain or shortness of breath while at rest or with mild exertion
• Been told by a doctor to only conduct physical activity under medical supervision
• Previous moderate to severe TBI
• < 8 days or >6 months following current complex mTBI
• Currently pregnant or become pregnant during study
• Currently involved in litigation associated with current or previous mTBI
• Currently on workman's compensation
• Previously participated in the study
• Previously received treatment at either site within last two years as this will unblind treatment group(s)

• Members of same household will not be included as they may determine their group assignment if more than one person from same household is included and assigned to different groups.

• Please note that participants with a history of mTBI, ADHD/LD, migraine, or motion sickness will NOT be excluded. We will adjust for any imbalance in the groups on these factors via covariate analysis.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 49 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Inova Health Care Services

OTHER

Sponsor Role: collaborator

United States Department of Defense

FED

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: lead

Responsible Party

Anthony P. Kontos, Ph.D.

Professor/Research Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anthony P Kontod, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Inova Health System - Inova Sports Medicine Concussion Program

Fairfax, Virginia, United States

Countries

United States

References

Zynda AJ, Trbovich AM, Kehinde F, Burley C, Collins MW, Okonkwo DO, Mucha A, Ostop S, Holland C, Perry C, Womble MN, Jennings S, Fedor S, Dollar C, Durfee KJ, Elbin RJ, Kontos AP. Role of anxiety in exercise intolerance and autonomic nervous system dysfunction post-concussion. Neurol Sci. 2025 Aug;46(8):3909-3918. doi: 10.1007/s10072-025-08204-9. Epub 2025 Apr 28.

Reference Type: DERIVED

PMID: 40293595 (View on PubMed)

Elbin RJ, Trbovich A, Womble MN, Mucha A, Fedor S, Stephenson K, Holland C, Dollar C, Sparto P, Durfee K, Patterson CG, Smith CN, Huppert TJ, Okonkwo DO, Collins MW, Kontos AP. Targeted multidomain intervention for complex mTBI: protocol for a multisite randomized controlled trial in military-age civilians. Front Neurol. 2023 Jun 30;14:1085662. doi: 10.3389/fneur.2023.1085662. eCollection 2023.

Reference Type: DERIVED

PMID: 37456641 (View on PubMed)

Other Identifiers

W81XWH2010745

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

PRO20050029

Identifier Type: -

Identifier Source: org_study_id