Phase 2 Randomized, Placebo-Controlled Clinical Trial of Recombinant Human Growth Hormone (rhGH) During Rehabilitation From Traumatic Brain Injury

Traumatic brain injury (TBI) is a major cause of death and disability, but there are currently no therapies with proven efficacy for optimizing regeneration of repair during rehabilitation. Using standard stimulation tests, as many as 40–50% of survivors of severe TBI have deficiency of one or more pituitary hormones. Of these, the somatotropic axis is the most commonly affected, with Growth Hormone (GH) deficiency affecting ~20% of persons with severe TBI. Treatment with recombinant human Growth Hormone (rhGH) is generally effective in reversing the effects of acquired GH deficiency, but there is no evidence documenting functional or neurocognitive improvement after GH replacement in TBI patients. As a consequence, screening for GH deficiency and GH replacement when deficiency is found is not routinely performed as part of the rehabilitation of TBI survivors. Given that most of the recovery after TBI occurs within the first 6–12 months after injury and IGF-1 and GH are part of a coordinated restorative neurotrophic system, we hypothesized that patients will optimally benefit from GH therapy during the window of maximal neuroregenerative activity. We performed a Phase IIa, randomized, double-blind, placebo-controlled feasibility trial of recombinant human Growth Hormone (rhGH), starting at discharge from an inpatient rehabilitation unit, with follow up at 6 and 12 months. Our primary hypothesis was that treatment with rhGH in the subacute period would result in improved functional outcomes 6 months after injury. Our secondary hypothesis proposed that treatment with rhGH would increase IGF-1 levels and be well tolerated. Sixty-three subjects were randomized, and 40 completed the trial. At baseline, there was no correlation between IGF-1 levels and peak GH levels after L-arginine stimulation. IGF-1 levels increased after rhGH treatment, but it took longer than 1 month for levels to be higher than for placebo-treated patients. rhGH therapy was well-tolerated. The rhGH group was no different from placebo in the Disability Rating Scale, Glasgow Outcome Scale-Extended, or neuropsychological function. However, a trend toward greater improvement from baseline in Functional Independence Measure (FIM) was noted in the rhGH treated group. Future studies should include longer treatment periods, faster titration of rhGH, and larger sample sizes

A randomized controlled trial protocol for people with traumatic brain injury enrolled in a healthy lifestyle program (GLB-TBI)

Weight gain is prevalent among people with traumatic brain injury (TBI) and may be attributable to environmental or injury-specific factors such as mobility impairment, endocrine dysfunction, behavioral and emotional disorders, and sensory loss. Few weight management programs exist to meet the unique needs of this population. Researchers modified a nationally recognized, evidence-based weight-loss program, Group Lifestyle Balance™ (GLB), to address the needs of over-weight and obese people post TBI (GLB-TBI). This current randomized controlled trial (RCT) examines the efficacy of the GLB-TBI on weight and secondary outcomes compared to an attention control educational support group. Furthermore, researchers have developed a mobile technology app to further engage participants in the program. This RCT will enroll and randomize 66 participants over a two-year period. It is anticipated that findings from this current RCT will contribute to the knowledge and evidence for an effective weight-loss intervention among this underserved population, with a goal of achieving full recognition by the Centers for Disease Control and Prevention-National Diabetes Prevention Program and subsequent Center for Medicare and Medicaid Services reimbursement for participation. Keywords: Physical activity, Nutrition, Weight loss, Rehabilitation, Interventio

A randomized controlled trial protocol for people with traumatic brain injury enrolled in a telehealth delivered diabetes prevention program (tGLB-TBI)

Obesity rates after traumatic brain injury (TBI) are high and are associated with greater risk of morbidity (diabetes, hypertension) and mortality when compared to the general population. Evidence-based interventions for this population are needed and our work modifying and examining the efficacy of the Diabetes Prevention Program Group Lifestyle Balance (GLB-TBI) are promising. Our recent randomized controlled trial included 57 adults with TBI who completed the GLB-TBI in-person and lost 17.8 ± 16.4lbs (7.9% body weight) compared to the attention control (0%). To broaden the accessibility of the intervention we will complete an RCT to assess the efficacy of telehealth delivery (tGLB-TBI) by enrolling 88 participants over a 3 year period. Results will provide a scalable telehealth weight-loss program that clinicians and community workers across the country can use to help people with TBI lose weight and improve health. The long-term goal is to reduce health inequities and broaden program dissemination to people with TBI that lack access due to environmental barriers, including living rurally or lacking transportation

Utilization of overground exoskeleton gait training during inpatient rehabilitation: a descriptive analysis

Abstract Background Overground exoskeleton gait training (OEGT) after neurological injury is safe, feasible, and may yield positive outcomes. However, no recommendations exist for initiation, progression, or termination of OEGT. This retrospective study highlights the clinical use and decision-making of OEGT within the physical therapy plan of care for patients after neurological injury during inpatient rehabilitation. Methods The records of patients admitted to inpatient rehabilitation after stroke, spinal cord injury, or traumatic brain injury who participated in at least one OEGT session were retrospectively reviewed. Session details were analyzed to illustrate progress and included: “up” time, “walk” time, step count, device assistance required for limb swing, and therapist-determined settings. Surveys were completed by therapists responsible for OEGT sessions to illuminate clinical decision-making. Results On average, patients demonstrated progressive tolerance for OEGT over successive sessions as shown by increasing time upright and walking, step count, and decreased assistance required by the exoskeleton. Therapists place preference on using OEGT with patients with more functional dependency and assess feedback from the patient and device to determine when to change settings. OEGT is terminated when other gait methods yield higher step repetitions or intensities, or to prepare for discharge. Conclusion Our descriptive retrospective data suggests that patients after neurological injury may benefit from OEGT during inpatient rehabilitation. As no guidelines exist, therapists’ clinical decisions are currently based on a combination of knowledge of motor recovery and experience. Future efforts should aim to develop evidence-based recommendations to facilitate functional recovery after neurological injury by leveraging OEGT

Improving Transition from Inpatient Rehabilitation following Traumatic Brain Injury: Protocol for the BRITE Pragmatic Comparative Effectiveness Trial

Moderate to severe traumatic brain injury (TBI) is a common cause of long-term disability. Due to challenges that include inconsistent access to follow-up care, persons with TBI being discharged from inpatient rehabilitation facilities (IRFs) are at risk for rehospitalization, poor reintegration into the community, family stress, and other unfavorable outcomes resulting from unmet needs. In a six-center randomized pragmatic comparative effectiveness study, the BRITE trial (Brain Injury Rehabilitation: Improving the Transition Experience, ClinicalTrials.gov NCT03422276), we compare the effectiveness of two existing methods for transition from IRF to community living or long-term nursing care. The Rehabilitation Discharge Plan (RDP) includes patient/family education and referrals for continued care. The Rehabilitation Transition Plan (RTP) provides RDP plus individualized, manualized care management via phone or videoconference, for 6 months. Nine hundred patients will be randomized (1:1) to RDP or RTP, with caregivers also invited to participate and contribute caregiver-reported outcomes. Extensive stakeholder input, including active participation of persons with TBI and their families, has informed all aspects of trial design and implementation planning. We hypothesize that RTP will result in better patient- and caregiver-reported outcomes (societal participation, quality of life, caregiver well-being) and more efficient use of healthcare resources at 6-months (primary outcome) and 12-months post-discharge, compared to RDP alone. Planned analyses will explore which participants benefit most from each transition model. With few exclusion criteria and other pragmatic features, the findings of this trial are expected to have a broad impact on improving transitions from inpatient TBI rehabilitation