Concussion, MildT-MDNCT04549532
Targeted Multidomain (T-MD) Interventions for Complex Mild Traumatic Brain Injury (mTBI)
A study testing Targeted Multidomain and Behavioral Management in people with Concussion, Mild, run by University of Pittsburgh at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 49 years
- Conditions the study is for
- Concussion, Mild
- What is being tested?
- Targeted Multidomain and Behavioral Management
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 169 participants
- Where
- 2 sitesUnited States
- Study dates
- 15 Jun 2021to 9 Apr 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 49 years
- All sexes
- No healthy volunteers
- Adult
Inclusion Criteria: Participants must meet ALL of the following 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: Participants will be excluded if they meet one or more of the following 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Inova Health System - Inova Sports Medicine Concussion Program
Fairfax, Virginia, 22031
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Multisite Randomized Controlled Trial of Targeted Multidomain (T-MD) Interventions for Complex Mild Traumatic Brain Injury (mTBI)
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.
Read the 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
- Being tested
- Targeted Multidomain, Behavioral Management
- Keywords
- concussion, mTBI
- Medical subject headings
- Brain Concussion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Targeted MultidomainBehavioural
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 ManagementBehavioural
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.
| Study group | Role | What they receive |
|---|---|---|
| T-MD Intervention Group | Experimental | 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. Receives: Behavioral: Targeted Multidomain |
| Behavioral Management | Active comparator | 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. Receives: Behavioral: Behavioral Management |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurobehavioral Symptom Inventory (NSI)
NSI is a 22 item symptom scale, participants will rate the severity of their symptoms on a 5 point likert scale (0, none/rarely ever present to 4, very severe, almost always present). The NSI total score is a sum of the 22 items (range 0-88).
Measured: NSI will be measured from baseline to 3 months.
Patient Global Impression of Change (PGIC)
PGIC is a self-reported assessment of change. Participants rate their impression of how much better they feel on a 7 point likert scale. It is a 1 item survey, with higher scores representing no change and associated with feeling worse. (Responses 1=much improved, 2=minimally improved, 3=no change, 4=minimally worse, 5=much worse, 6=very much worse).
Measured: The PGIC will be measured from baseline to 3 months.
Functional Near-infrared Spectroscopy (fNIRS)
fNIRS will be used to record changes in oxygenated hemoglobin (activation) and deoxygenated hemoglobin (deactivation) in participants. fNIRS will assess 3 broad regions of interest: left and right temporal, occipital. It will measure bilateral areas of the inferior frontal, dorsal-lateral prefrontal, and frontal regions of the brain including Brodmann areas as well as the middle frontal gyrus, superior temporal gyrus, and extrastriate visual cortical regions. fNIRS will be done in 2 different paradigms: 1) at rest, and 2) during cognitive activity. At rest measurements will occur while participants are seated, and last about 2 minutes. For the cognitive activity, participants will perform the ImPACT test while wearing the fNIRS unit, and last 20 minutes. We will compare brain activation and deactivation in ROIs across the two points and between rest and cognitive activity paradigms. We will also examine task specific changes within the cognitive test paradigm.
Measured: fNIRS will be conducted two times, once baseline and again at the 4 week visit.
Secondary outcomes (13)
Behavioral Symptom Inventory (BSI-18)
The BSI is an 18 item symptom inventory that assesses the level of psychological distress during the past 7 days. Responses are on a 5 point Likert scale (0=not at all - 4 = extremely). The BSI-18 yields total global severity index ranging from 0-72, as well as somatic, depression and anxiety sub-scales. Higher scores indicate higher levels of psychological distress.
Measured: The BSI-18 will be measured from baseline to 3 months.
Dizziness Handicap Inventory (DHI)
The DHI is a 25 item self-reported measure that examines dizziness-related handicap. The assessment has 3 domains (functional, emotional, and physical). Participants self-report the level dizziness has impacted their abilities in the 3 domains with each domain having 9 questions (questions are answered No (0)/Sometimes(2)/Yes(4)) Item scores are summed. There is a maximum score of 100 (28 points for physical, 36 points for emotional and 36 points for functional). Minimum score is 0.
Measured: The DHI will be measured from baseline to 3 months.
Vestibular Ocular Motor Screening (VOMS)
The VOMS assesses impairment via patient report symptom provocation following each of 5 test components (smooth pursuits, horizontal/vertical saccades, convergence, horizontal and vertical vestibular ocular reflex (VOR) and visual motor sensitivity (VMS). Patients verbally rate changes in headache, dizziness, nausea, and fogginess after each test, as well as report their baseline symptoms. Symptoms in each area are rated on scale 0 (none) to 10 (severe). Scores on any VOMS item of 2+ reflects a positive screening cut-off for vestibular and/or ocular motor impairment.
Measured: VOMS will be will be measured from baseline to 4 weeks.
Modified Balance Error Scoring System (mBESS)
The mBESS measures postural stability and consists of three stances including feet side by side, a tandem stance, and a single-leg stance on the non-dominant leg. The three stances are performed for 20 seconds each and completed with eyes closed and hand on the iliac crests. Errors include lifting hands off the iliac crests, opening the eyes, stepping, stumbling, or falling, moving the hip into more than a 30 degree of flexion or abduction, lifting the forefoot or heel, or remaining out of the testing position for more than 5 seconds. Each error equals 1 point, with higher scores indicating worse performance. Score ranges from 0-30 (maximum of 10 errors per each stance).
Measured: mBESS will be measured from baseline to 4 weeks.
Functional Gait Assessment (FGA)
FGA is 10 items that assesses the ability of participants to walk with head turns, changes of speed of walking, and walking around obstacles. Each item is scored on a 4 point ordinal scale; 0 (severe impairment), 1 (moderate impairment), 2 (mild impairment), 3 (normal ambulation). Score range is 0-30.
Measured: The FGA will be measured from baseline to 4 weeks.
Clinical Profile Screening Inventory (CP Screen)
The CP Screen is a 29 item self-report, clinical profiles based symptom inventory that measures five concussion clinical profiles: 1) anxiety/mood, 2)cognitive/fatigue, 3) migraine, 4) ocular, 5) vestibular; and two modifying factors sleep and cervical. Participants indicate on a scale of 0 (none) to 3 (severe) the level of symptom severity for each item. The CP screen yields an average factor and modifier scores, with higher scores indicative of worse symptom severity, score range is 0-87.
Measured: The CP screen will be measured from baseline to 3 months.
Immediate Post-concussion Assessment and Cognitive Testing (ImPACT)
ImPACT will be used to assess neurocognitive performance. ImPACT is a computerized neurocognitive test that includes 6 modules: 1) verbal memory, 2) design memory, 3) X's and O's, 4) symbol matching, 5) color matching, and 6) three letter memory. These modules are used to form/score four composite scores - verbal and visual memory 5), visual motor processing speed 6), and reaction time (seconds).
Measured: ImPACT will be administered at baseline, 2 week, 4 week visits.
Pittsburgh Sleep Quality Index (PSQI)
The PSQI assesses sleep quality. It is an 19 item self-reported measure that is comprised of seven component scores: 1) subjective sleep quality, 2) sleep latency, 3) sleep duration, 4) sleep efficiency, 5) sleep disturbances, 6) sleep medication usage, and 7) daytime dysfunction. Each item is scored 0-3 (0 = very good, 1 = fairly good, 2= fairly bad, 3=very bad). Higher scores indicate more sleep dysfunction. Score range is 0-21.
Measured: The PSQI will be measured from baseline to 3 months.
Headache Impact Test (HIT-6)
The HIT-6 is comprised of 6 self-report items that assess frequency, severity and limitations of daily activities, fatigue, irritability, and concentration related to headaches. Items score from 6 to 13, with higher scores indicating worse severity. Scores = never = 6pts, rarely = 8 pts, sometimes = 10pts, very often = 11 pts, always = 13 points. Score range 36-78.
Measured: The HIT-6 will be measured from baseline to 3 months.
ID Migraine
The ID Migraine will be used to screen for headache symptoms. It is a 3 item screening tool designed to assess presence (yes/no) of symptoms related to headache/migraine pain. Scores range from 0-3 with clinical cut-off of 2+ indicating presence of migraines.
Measured: ID Migraine will be measured from baseline to 3 months.
Short Form McGill Pain Questionnaire (SF-MPQ)
The SF-MPQ is a 15 item pain scale in which participants rate the intensity of their pain on a 4 point likert scale 0 (none) to 3 (severe). The assessment has two subscales (sensory and affective). Higher scores indicate higher pain. Score range 0-75.
Measured: The SF-MPQ will be measured from baseline to 3 months.
International Physical Activity Questionnaire (IPAQ)
The International Physical Activity Questionnaire (IPAQ) will be used to assess potential treatment group differences in activity level. The IPAQ is a validated tool to assess recall of average activity level and intensity over the preceding 7 days. Activity levels can be expressed as categorical variables (low, medium, high activity levels) or a continuous variable (MET-minutes/week).
Measured: The IPAQ will be measured from baseline to 3 months.
Buffalo Concussion Treadmill Test (BCTT)
The BCTT will be used in this study to measure autonomic dysfunction of participants' following mTBI. Prior to test initiation, resting heart rate (HR) is measured after a 2 minute seated resting period. A visual analog scale is used to rate symptoms at baseline.
Measured: The BCTT will be completed at 2 study timepoints (baseline and 4 weeks).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2020
- Study start15 Jun 2021
- Primary completion30 Apr 2024
- Study completion9 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Concussion, MildStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Design: The current study will employ a single blinded, two-group repeated measures (baseline, 2-week, 4-week, 3-month) design with permuted block random assignment to T-MD and usual care intervention groups.
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 169 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Inova Health Care Services, United States Department of Defense
- Responsible party
- Principal investigator, Anthony P. Kontos, Ph.D., University of Pittsburgh
- Investigators
- Anthony P Kontod, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04549532
- Sponsor's protocol ID
- PRO20050029
- Other IDs
- W81XWH2010745
- Acronym
- T-MD
- Status last verified
- Oct 2025
- First submitted
- 8 Sep 2020
- Last updated
- 9 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Per DoD grant requirement, de-identified data will be shared with the Federal Interagency Traumatic Brian Injury Research (FITBIR) informatics system and Congressionally Directed Medical Research Programs (CDMRP).
Publications
Kontos AP, Collins MW, Okonkwo DO, Zynda AJ, Patterson CG, Smith C, Trbovich AM, Mucha A, Soose R, Sparto PJ, Holland CL, Womble M, Jennings S, Fedor S, Dollar CM, Durfee KJ, Elbin RJ. Targeted Multidomain Treatment for Mild Traumatic Brain Injury: A Randomized Clinical Trial. JAMA Netw Open. 2026 Mar 2;9(3):e261317. doi: 10.1001/jamanetworkopen.2026.1317.
PubMed 41817527Zynda 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.
PubMed 40293595Elbin 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.
PubMed 37456641
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multisite Randomized Controlled Trial of Targeted Multidomain (T-MD) Interventions for Complex Mild Traumatic Brain Injury (mTBI)
- ClinicalTrials.gov ID
- NCT04549532
- Acronym / sponsor ID
- T-MD / PRO20050029
- Conditions
- Concussion, Mild
- Keywords
- concussion, mTBI
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 169 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- Inova Health Care Services, United States Department of Defense
- Study start
- 15 Jun 2021 (actual)
- Primary completion
- 30 Apr 2024 (actual)
- Study completion
- 9 Apr 2025 (actual)
- First posted
- 16 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
- Model description
- Design: The current study will employ a single blinded, two-group repeated measures (baseline, 2-week, 4-week, 3-month) design with permuted block random assignment to T-MD and usual care intervention groups.
| Arm | Type | Receives |
|---|---|---|
| T-MD Intervention Group | Experimental | Behavioral: Targeted MultidomainParticipants 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. |
| Behavioral Management | Active comparator | Behavioral: Behavioral ManagementParticipants 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. |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Targeted MultidomainParticipants 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. | Behavioural | T-MD Intervention Group |
| Behavioral Management1.3. 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. | Behavioural | Behavioral Management |
Primary outcome
Neurobehavioral Symptom Inventory (NSI)
Time frame: NSI will be measured from baseline to 3 months.
NSI is a 22 item symptom scale, participants will rate the severity of their symptoms on a 5 point likert scale (0, none/rarely ever present to 4, very severe, almost always present). The NSI total score is a sum of the 22 items (range 0-88).
Patient Global Impression of Change (PGIC)
Time frame: The PGIC will be measured from baseline to 3 months.
PGIC is a self-reported assessment of change. Participants rate their impression of how much better they feel on a 7 point likert scale. It is a 1 item survey, with higher scores representing no change and associated with feeling worse. (Responses 1=much improved, 2=minimally improved, 3=no change, 4=minimally worse, 5=much worse, 6=very much worse).
Functional Near-infrared Spectroscopy (fNIRS)
Time frame: fNIRS will be conducted two times, once baseline and again at the 4 week visit.
fNIRS will be used to record changes in oxygenated hemoglobin (activation) and deoxygenated hemoglobin (deactivation) in participants. fNIRS will assess 3 broad regions of interest: left and right temporal, occipital. It will measure bilateral areas of the inferior frontal, dorsal-lateral prefrontal, and frontal regions of the brain including Brodmann areas as well as the middle frontal gyrus, superior temporal gyrus, and extrastriate visual cortical regions. fNIRS will be done in 2 different paradigms: 1) at rest, and 2) during cognitive activity. At rest measurements will occur while participants are seated, and last about 2 minutes. For the cognitive activity, participants will perform the ImPACT test while wearing the fNIRS unit, and last 20 minutes. We will compare brain activation and deactivation in ROIs across the two points and between rest and cognitive activity paradigms. We will also examine task specific changes within the cognitive test paradigm.
13 secondary outcomes
Behavioral Symptom Inventory (BSI-18)
Time frame: The BSI-18 will be measured from baseline to 3 months.
Dizziness Handicap Inventory (DHI)
Time frame: The DHI will be measured from baseline to 3 months.
Vestibular Ocular Motor Screening (VOMS)
Time frame: VOMS will be will be measured from baseline to 4 weeks.
Modified Balance Error Scoring System (mBESS)
Time frame: mBESS will be measured from baseline to 4 weeks.
Functional Gait Assessment (FGA)
Time frame: The FGA will be measured from baseline to 4 weeks.
Clinical Profile Screening Inventory (CP Screen)
Time frame: The CP screen will be measured from baseline to 3 months.
Immediate Post-concussion Assessment and Cognitive Testing (ImPACT)
Time frame: ImPACT will be administered at baseline, 2 week, 4 week visits.
Pittsburgh Sleep Quality Index (PSQI)
Time frame: The PSQI will be measured from baseline to 3 months.
Headache Impact Test (HIT-6)
Time frame: The HIT-6 will be measured from baseline to 3 months.
ID Migraine
Time frame: ID Migraine will be measured from baseline to 3 months.
Short Form McGill Pain Questionnaire (SF-MPQ)
Time frame: The SF-MPQ will be measured from baseline to 3 months.
International Physical Activity Questionnaire (IPAQ)
Time frame: The IPAQ will be measured from baseline to 3 months.
Buffalo Concussion Treadmill Test (BCTT)
Time frame: The BCTT will be completed at 2 study timepoints (baseline and 4 weeks).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2025.
- Derived from this study: PubMed 41817527Kontos AP, Collins MW, Okonkwo DO, Zynda AJ, Patterson CG, Smith C, Trbovich AM, Mucha A, Soose R, Sparto PJ, Holland CL, Womble M, Jennings S, Fedor S, Dollar CM, Durfee KJ, Elbin RJ. Targeted Multidomain Treatment for Mild Traumatic Brain Injury: A Randomized Clinical Trial. JAMA Netw Open. 2026 Mar 2;9(3):e261317. doi: 10.1001/jamanetworkopen.2026.1317.
- Derived from this study: PubMed 40293595Zynda 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.
- Derived from this study: PubMed 37456641Elbin 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.
- Individual participant dataSharing planned: Yes. Per DoD grant requirement, de-identified data will be shared with the Federal Interagency Traumatic Brian Injury Research (FITBIR) informatics system and Congressionally Directed Medical Research Programs (CDMRP).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anthony P Kontod, PhD principal investigator
University of Pittsburgh
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Targeted Multidomain and Behavioral Management in people with Concussion, Mild, run by University of Pittsburgh at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Neurobehavioral Symptom Inventory (NSI) (time frame: NSI will be measured from baseline to 3 months.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04549532, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2025.