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

NCT04549532 | Completed DMC

• 2 other identifiers: PRO20050029W81XWH2010745
• Study Type: interventional
• Target: 169
• Locations: 1 country
• Sites: 2

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.

Conditions

Concussion, Mild

Keywords

concussion; mTBI

Outcome Measures

Primary Outcomes (3)

• 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).

  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).

  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.

  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-18 will be measured from baseline to 3 months.

• Dizziness Handicap Inventory (DHI)

  The DHI will be measured from baseline to 3 months.

• Vestibular Ocular Motor Screening (VOMS)

  VOMS will be will be measured from baseline to 4 weeks.

• Modified Balance Error Scoring System (mBESS)

  mBESS will be measured from baseline to 4 weeks.

• Functional Gait Assessment (FGA)

  The FGA will be measured from baseline to 4 weeks.

Study Arms (2)

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.

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.

Behavioral: Behavioral Management

Interventions

Targeted Multidomain 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.

T-MD Intervention Group

Behavioral Management 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.

Behavioral Management

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pittsburgh: lead
• Inova Health Care Services: collaborator
• United States Department of Defense: collaborator

Study Sites (2)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Inova Health System - Inova Sports Medicine Concussion Program

Fairfax, Virginia, 22031, United States

Location

Related Publications (2)

• 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.

  PMID: 40293595 DERIVED

• 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.

  PMID: 37456641 DERIVED

MeSH Terms

Conditions

Brain Concussion

Condition Hierarchy (Ancestors)

Brain Injuries, Traumatic; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds and Injuries; Wounds, Nonpenetrating

Study Officials

• Anthony P Kontod, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor/Research Director

Model Details: 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.

Study Record Dates

• First Submitted: September 8, 2020
• First Posted: September 16, 2020
• Study Start: June 15, 2021
• Primary Completion: April 30, 2024
• Study Completion: April 9, 2025
• Last Updated: October 9, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Time Frame: De-identified data will be shared with FITBIR on an annual basis as required by the funder (DoD).
• Access Criteria: Formal requests must be submitted and approved to FITBIR to access this study's de-identified data.

Locations

US (2)