Clinical trial NCT04549532: Targeted Multidomain (T-MD) Interventions for Complex Mild Traumatic Brain Injury (mTBI)
Official title: Multisite Randomized Controlled Trial of Targeted Multidomain (T-MD) Interventions for Complex Mild Traumatic Brain Injury (mTBI)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Concussion, Mild
Keywords: concussion
mTBI
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Inova Health Care Services
name: United States Department of Defense
First posted: 2020-09-16
Enrollment: 169
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Neurobehavioral Symptom Inventory (NSI)
timeFrame: NSI will be measured from baseline to 3 months.
measure: Patient Global Impression of Change (PGIC)
timeFrame: The PGIC will be measured from baseline to 3 months.
measure: Functional Near-infrared Spectroscopy (fNIRS)
timeFrame: fNIRS will be conducted two times, once baseline and again at the 4 week visit.
Secondary outcomes:
measure: Behavioral Symptom Inventory (BSI-18)
timeFrame: The BSI-18 will be measured from baseline to 3 months.
measure: Dizziness Handicap Inventory (DHI)
timeFrame: The DHI will be measured from baseline to 3 months.
measure: Vestibular Ocular Motor Screening (VOMS)
timeFrame: VOMS will be will be measured from baseline to 4 weeks.
measure: Modified Balance Error Scoring System (mBESS)
timeFrame: mBESS will be measured from baseline to 4 weeks.
measure: Functional Gait Assessment (FGA)
timeFrame: The FGA will be measured from baseline to 4 weeks.
measure: Clinical Profile Screening Inventory (CP Screen)
timeFrame: The CP screen will be measured from baseline to 3 months.
measure: Immediate Post-concussion Assessment and Cognitive Testing (ImPACT)
timeFrame: ImPACT will be administered at baseline, 2 week, 4 week visits.
measure: Pittsburgh Sleep Quality Index (PSQI)
timeFrame: The PSQI will be measured from baseline to 3 months.
measure: Headache Impact Test (HIT-6)
timeFrame: The HIT-6 will be measured from baseline to 3 months.
measure: ID Migraine
timeFrame: ID Migraine will be measured from baseline to 3 months.
measure: Short Form McGill Pain Questionnaire (SF-MPQ)
timeFrame: The SF-MPQ will be measured from baseline to 3 months.
measure: International Physical Activity Questionnaire (IPAQ)
timeFrame: The IPAQ will be measured from baseline to 3 months.
measure: Buffalo Concussion Treadmill Test (BCTT)
timeFrame: The BCTT will be completed at 2 study timepoints (baseline and 4 weeks).
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Fairfax
country: United States
facility: Inova Health System - Inova Sports Medicine Concussion Program
state: Virginia
Study officials:
affiliation: University of Pittsburgh
name: Anthony P Kontod, PhD
role: PRINCIPAL_INVESTIGATOR
References: