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Appendix C Recent and Ongoing Clinical Trials: CRT for TBI The following table includes recent and ongoing clinical trials related to cognitive rehabilitation therapy and traumatic brain injury; these trials may include criteria that go beyond the scope and methods used by the IOM committee in its evaluation of the current evidence. The trials are listed in alphabetical order, with start and end dates ranging from 1996 to 2013. The table was created based on information from ClinicalTrials.gov, a service of the National Institutes of Health (NIH). 287
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288 COGNITIVE REHABILITATION THERAPY FOR TBI Study Title, Sponsor, and Principle Investigator Study Purpose and Detailed Description 15 Year Longitudinal Phase 1: (Surveillance) DVBIC is collaborating with the Defense Man- Study of TBI Incurred power Data Center (DMDC) to assess mortality surveillance of OIF/OEF by Members of the veterans to determine whether an in-theatre history of TBI increases risk Armed Forces in OIF/ of death among OIF/OEF veterans. DMDC obtains data from a variety OEF of federal sources including information from the Social Security Admin- istration’s Death Master File and deceased benefit information from Vet- erans’ Affairs. To date, DMDC has identified approximately 1.5 million Defense and Veterans service members who have served in OIF/OEF of which over 15,000 are Brain Injury Center no longer alive as of March 2011. PI: COL Michael Regarding those deaths, DVBIC is in the process of (a) determining cause Lewis, M.D. of death; and (b) history of TBI. A series of statistical analyses will be performed on the data to identify possible trends within the data in an effort to determine factors that may have preventive benefit. Phase 2: (Previous TBI Diagnosis) is submitting its protocol as an amend- ment to the Natural History protocol (Phase 3). Phase 2 is designed to collect neurobehavioral information on service members and veterans who are 12 months or more post-TBI diagnosis (dating back to October 2001), as well as trauma controls and healthy controls. Phase 2 includes a second protocol addressing health related quality of life in family care- givers of service members and veterans with TBI. The caregiver protocol will be submitted to OHSP for review last month. Phase 3: (Incident TBI) has received approval for the Natural History protocol from the WRAMC and USUHS IRBs. Recruitment began at WRAMC in May 2011. The study is designed to collect comprehensive pathophysiologic, neurobehavioral, and neuroimaging information on service members newly diagnosed with TBI, trauma controls, and healthy controls. Annual follow-up brief evaluations will be done and intermit- tently will include a comprehensive examination similar to baseline. Study Purpose: To learn more about behavior and everyday functioning Acute Cognitive and Neurobehavioral after brain injury, and to learn if behavior and functioning gets better Intervention: Efficacy with more education about changes after brain injury. Evaluation Detailed Description: To evaluate the efficacy of the First Steps interven- tion for improving neurobehavioral functioning, functional status, and life Virginia satisfaction, and for increasing knowledge about TBI and compensatory Commonwealth strategies. The First Steps program was developed to address the neurobe- University; U.S. havioral and emotional concerns of survivors of TBI during the course Department of of inpatient rehabilitation. Program format and content reflects clinical Education experience and extensive research review. Input from survivors, family PI: Jeffrey S. Kreutzer, members, and rehabilitation staff trained in working with the TBI popula- Ph.D. tion has also helped shape the implementation protocol. The foundation of the protocol is a curriculum [Niemeier, J., Kreutzer, J., & Taylor, L. (2005). Acute cognitive and neurobehavioral intervention for individuals with acquired brain injury: Preliminary outcome data. Neuropsychological Rehabilitation, 15(2), 129–146.] The First Steps curriculum consists of 10 lessons and was developed to address the common needs, issues, and con- cerns of TBI survivors admitted acutely for inpatient rehabilitation.
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289 APPENDIX C Sample Description Study Type Study Design Time Frame Phase I: Observational • Primary Purpose: 2007 Start All OIF/OEF Veteran Observational Service Members since October 2001 Gender: Both Group: Adult Phase II: TBI: N = 1,600 Trauma Controls: N = 800 Healthy Controls: N = 800 Gender: Both Group: Adult Phase III: Focus Groups: N = 60 Cognitive Interviews: N = 60 Longitudinal Online Questionnaire: N = 300 Gender: Both Group: Adult N = 103 Observational • Observational October 2002– Model: Cohort October 2008 Gender: Both • Time Perspective: Prospective Group: Adult/Senior
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290 COGNITIVE REHABILITATION THERAPY FOR TBI Study Title, Sponsor, and Principle Investigator Study Purpose and Detailed Description Study Purpose: More than 1.4 million people a year in the United States Acute Neurobehav- ioral Program for begin confronting life with the medical, cognitive, and psychosocial chal- Improving Functional lenges resulting from traumatic brain injury (TBI). A range of cognitive Status After TBI impairments commonly observed following injury increase caregiver bur- den as well as per-person lifetime costs for care and support of survivors of TBI, estimated at $600,000 to $1,875,000. Our long-term goal is to Virginia lessen these burdens through improving the functional status of patients Commonwealth with TBI by providing an evidence-based, comprehensive, brief, acute- University; Eunice care intervention, First Steps Acute Neurobehavioral and Cognitive In- Kennedy Shriver tervention (FANCI). The 10-sesson, manualized FANCI Program will be National Institute of tested in a controlled, randomized study. Therapeutic components of the Child Health and FANCI include didactics, cognitive remediation, demonstration, guided Human Development self-reflection, rehearsal, and supported practice of skills and strategies. (NICHD) Specific hypotheses are that (1) FANCI will result in more improvement PI: Janet P. Niemeier, in functional status compared to standard interdisciplinary rehabilitation Ph.D. treatment and (2) FANCI will result in more improvement on measures of neurobehavioral functioning compared to standard rehabilitation care for patients with moderate to severe TBI. We base these hypotheses on the ob- servations that (1) providing information about symptoms, treatment, and coping results in reduced symptom intensity and duration for patients with TBI, and (2) inpatient participants in recent FANCI pilot studies learned > 80% of the FANCI Program curriculum, and (3) the most recent pilot study participants had significantly better functional outcomes at discharge than matched controls. The specific aims of the proposed study are to (1) evaluate the efficacy of FANCI for improving functional status following treatment using the FIM, (2) examine the impact of FANCI on broader outcome measures of general emotional and behavioral functioning and productive activity in the community as measured post-treatment and at 6-month follow-up, (3) examine contributions of participant injury sever- ity and cognitive status at time of treatment to treatment outcome and treatment response, (4) examine contributions of treatment variables of session topic and mastery, caregiver presence, and concurrent therapies on treatment outcome and treatment response for inpatients with TBI. Primary outcome measure is the (FIM). We will secondarily compare scores on the Disability Rating Scale (DRS), Glasgow Outcome Scale- Extended (GOSE), Rehabilitation Intensity of Therapy Scale (RITS), and Frontal Systems Behavior Scale (FRsBe). Our design is a parallel groups, single-blind, randomized, controlled trial. We will enroll 150 (75 treatment, 75 control) participants. Inclusion Criteria: Mod. to Sev. TBI based on time to commands, English speaker, Length of stay ≥ 5 days in acute BI rehabilitation Unit, 18 years of age or older, ≥ 79 on GOAT. Detailed Description: N/A
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291 APPENDIX C Sample Description Study Type Study Design Time Frame N = 150 Interventional • Allocation: March 2008– Randomized September 2013 Gender: Both • Control: Placebo Control Group: Adult/Senior • Endpoint Classification: Efficacy Study • Intervention Model: Parallel Assignment • Masking: Double Blind (Investigator, Outcomes Assessor) • Primary Purpose: Treatment
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292 COGNITIVE REHABILITATION THERAPY FOR TBI Study Title, Sponsor, and Principle Investigator Study Purpose and Detailed Description Study Purpose: Patients with traumatic brain injury often experience Amantadine for Treat- ment of Symptoms of a period of acute confusion that may include agitation as they recover the Post-Traumatic from their injuries. While this confusion generally resolves with time, Confusional State patients may pose increased risk of injury to themselves or others during this period. Their behavior may also increase stress for family members and interfere with their ability to benefit from rehabilitation therapies. Methodist A number of different medications have been used to treat confusion to Rehabilitation decrease agitation, decrease risk of injury, and improve participation in Center; U.S. Depart- rehabilitation therapies. To this point, there has not been a research or ment of Education scientific basis for knowing which medication is the best for a specific PI: Stuart A. Yablon, patient. The overall goal of this study is to conduct a scientific investiga- M.D. tion to help determine which medication works best to treat confusion. Detailed Description: Patients with TBI who require inpatient rehabilita- tion are frequently confused at the time of admission for rehabilitation. Our investigations of confusion conducted as part of the TBIMSM have clarified the nature of confusion in early recovery after TBI. Early confu- sion (PTCS) has been found to be a complex syndrome characterized by disorientation, cognitive impairment, restlessness, decreased level of day- time arousal, sleep disturbance, fluctuation of symptoms, and psychotic- type symptoms. PTCS complicates early management of patients with TBI, and may contribute to increased risk of injury to patients and hos- pital staff, increased stress among family members and staff, decreased participation in therapies, increased cost of care, and an increased likeli- hood of being discharged to psychiatric or long-term care settings. These facts indicate the need for effective management of PTCS. Consensus regarding optimal treatment of the cognitive and behavioral symptoms encountered among patients with PTCS does not exist currently. While many agents have been tried to address such symptoms in TBI, few have been investigated systematically. These circumstances indicate the need for appropriate clinical trials to provide guidance to clinicians for medi- cal treatment of PTCS. In response, the NIDRR-Traumatic Brain Injury Model System of Mississippi proposed a randomized, double-blinded, placebo-controlled, parallel group trial for the pharmacological treat- ment of PTCS. The agent selected for this clinical trial is amantadine, an NMDA and indirect dopamine agonist. This agent will be compared to placebo on response measures of efficacy and safety. Study hypothesis: Amantadine will reduce the severity and number of symptoms of PTCS.
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293 APPENDIX C Sample Description Study Type Study Design Time Frame N = 79 Interventional • Allocation: April 2003– Randomized June 2008 Gender: Both • Control: Placebo Control Group: Child/Adult/ • Endpoint Senior Classification: Efficacy Study • Intervention Model: Parallel Assignment • Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) • Primary Purpose: Treatment
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294 COGNITIVE REHABILITATION THERAPY FOR TBI Study Title, Sponsor, and Principle Investigator Study Purpose and Detailed Description Study Purpose: This study investigates how well a new therapy program An Intervention Program to Reduce prevents persistent symptoms (e.g., headaches, fatigue, irritability, etc.) to the Risk of after concussion. The program involves examining beliefs about concus- Persistent Symptoms sion and learning healthy coping strategies, and is completed with the After Concussion first three months post-injury. Detailed Description: Although the majority of patients with mild trau- University of British matic brain injury (MTBI) experience complete recovery within three Columbia months, a sizeable group continues to report frequent and severe symp- PI: Noah Silverberg, toms such as headaches, fatigue, difficulty concentrating, forgetfulness, Ph.D. and irritability, in what is labeled persistent post-concussion syndrome (PCS). Persistent PCS is associated with vocational, recreational, and social disability. Early education and reassurance (treatment as usual) is effective in general, but appears insufficient for this subgroup. Recent re- search has identified risk factors for persistent PCS, including inaccurate illness beliefs, maladaptive coping behavior, and emotional distress. The present study will evaluate the additive efficacy of a cognitive-behavioral therapy protocol designed to modify these risk factors, over and above treatment as usual. Participants with MTBI will be recruited within 6 weeks of injury. Those identified as being at-risk for persistent PCS based on evidence-based criteria will receive treatment as usual and then be randomly assigned to receive either no further intervention or cognitive- behavioral therapy. We hypothesize that the group receiving cognitive- behavioral therapy will have fewer PCS symptoms and be less disabled at follow-up. We also hypothesize that compensation-seeking status will mitigate this improvement and that illness beliefs, coping behavior, and emotional distress will mediate this improvement. A blinded rater will conduct the baseline and outcome assessments. Study Purpose: Memory deficits are common after traumatic brain inju- Behavioral and Neuroimaging ries (TBIs) and are characteristic of various forms of dementia, such as Changes After Alzheimer’s disease and its common precursor mild cognitive impairment Cognitive Rehab in (MCI). This project intends to assess the efficacy of cognitive rehabilita- Traumatic Brain tion in these patient populations. We will also use neuroimaging (func- Injuries (TBI) and Mild tional magnetic resonance imaging [fMRI]) to assess changes in brain Cognitive Impairment activity that occurs following cognitive rehabilitation. (MCI) Detailed Description: N/A Department of Veterans Affairs; Emory University PI: Benjamin M. Hampstead, Ph.D.
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295 APPENDIX C Sample Description Study Type Study Design Time Frame N = 65 Interventional • Allocation: June 2009–April Randomized 2011 Gender: Both • Control: Active Control Group: Adult • Endpoint Classification: Efficacy Study • Intervention Model: Parallel Assignment • Masking: Single Blind (Subject) • Primary Purpose: Prevention N = 60 Interventional • Allocation: Randomized July 2008–June • Control: Active 2013 Gender: Both Control • Endpoint Group: Adult/Senior Classification: Efficacy Study • Intervention Model: Parallel Assignment • Masking: Single Blind (Subject) • Primary Purpose: Treatment
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296 COGNITIVE REHABILITATION THERAPY FOR TBI Study Title, Sponsor, and Principle Investigator Study Purpose and Detailed Description Study Purpose: The purpose of this study is to determine whether an inves- CDP-Choline and Working Memory tigational drug, called “CDP-Choline,” improves memory in people with After TBI: A Neuroim- traumatic brain injury (TBI). To do this, we are asking for people with aging Study traumatic brain injury and people without traumatic brain injury to be a part of this study. We will compare results between each group to see if this investigational drug makes a difference with memory. We will also compare University of Pitts- brain imaging results and information collected before and after the taking burgh; National Insti- of the study medication to see if there are any differences. We hypothesize tutes of Health (NIH); that there will be differences in brain activation patterns between individu- Eunice Kennedy als with TBI and healthy controls, as well as differences in performance on Shriver National In- memory testing at baseline. We further hypothesize that, after treatment stitute of Child Health with CDP-Choline, the patterns in neuroimaging findings and cognitive test- and Human Develop- ing results for individuals with TBI will more closely resemble results ob- ment (NICHD) served for healthy individuals. We hope that what we learn from this study PI: Patricia M. Arenth, will be helpful in the future treatment of individuals with head injury. Ph.D. Detailed Description: Despite the prevalence of working memory deficits following traumatic brain injury (TBI), the scientific data regarding phar- macological treatment of this problem is limited. As deficits in working memory are known to have a significant impact on functional outcomes for individuals with TBI, further research in this area is essential in or- der for physicians to be able to treat this problem more effectively. The primary goal of the proposed project is to examine the efficacy of a par- ticular pharmacological agent, CDP-Choline, in the treatment of working memory deficits following traumatic brain injury (TBI). The study sample will consist of 48 subjects: A group of 24 individuals who have sustained moderate to severe TBI, and a group of 24 healthy controls. Each group will be divided into a placebo and treatment group. The project will utilize functional Magnetic Resonance Imaging (fMRI) to investigate the cerebral neurophysiological effects of treatment with CDP-Choline. A working memory task (N-Back) will be employed during fMRI sessions. In addi- tion, the effects of treatment with CDP-Choline on neuropsychological testing performance will also be evaluated, and the correlations between behavioral performance and neuroimaging results will be observed. We will achieve these goals by comparing baseline neuropsychological testing results as well as fMRI results, with a second set of testing and neuroim- aging results obtained following 1 month of pharmacological treatment with CDP Choline or placebo. Based on our preliminary studies and the available literature, we expect to see the following: Baseline fMRI results are expected to show that individuals with TBI display altered patterns of cerebral activation during a working memory task, as compared to healthy controls. With CDP-Choline treatment, we expect TBI subjects to display fMRI laterality and dispersion patterns that more closely resemble patterns of healthy controls. In addition, we anticipate improvements in behavioral performance on both the specific working memory task (N-Back), and on traditional neuropsychological tests to be associated with CDP-Choline treatment, with greater magnitude of change on testing results for the TBI group as compared to any changes noted for the control or placebo groups. Finally, we anticipate that specific significant correlations will be observed between neuropsychological testing results and neuroimaging findings, and that the strength of these relationships will be greater for the TBI treatment group, as compared to the placebo or healthy control groups. By conducting the proposed study in this manner, we hope to pro- vide scientific data that will allow for improved treatment, and ultimately improved functional outcomes for individuals who have sustained TBI.
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297 APPENDIX C Sample Description Study Type Study Design Time Frame N = 48 Interventional • Allocation: March 2009– Randomized August 2012 Gender: Both • Control: Placebo Control Group: Adult • Endpoint Classification: Efficacy Study • Intervention Model: Parallel Assignment • Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) • Primary Purpose: Treatment
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314 COGNITIVE REHABILITATION THERAPY FOR TBI Study Title, Sponsor, and Principle Investigator Study Purpose and Detailed Description Study Purpose: The purpose of this study is to determine whether mind- Mindfulness-Based Cognitive Therapy fulness-based cognitive therapy is effective in reducing depression symp- Intervention to Treat toms in individuals who have experienced a traumatic brain injury. The Depression in investigators hypothesize that participants who are given the 10-week Individuals with a intervention will have fewer depression symptoms than the participants Traumatic Brain Injury in the control group, and this improvement will be maintained at the 3-month follow-up assessment. Lakehead University; Detailed Description: Major depression is a significant chronic problem Ontario Neurotrauma for people with traumatic brain injury (TBI), and its treatment is dif- Foundation ficult. A promising approach to treat depression is mindfulness-based PI: Michel Bédard, cognitive therapy (MBCT), a relatively new therapeutic approach rooted Ph.D. in mindfulness-based stress-reduction (MBSR) and cognitive behavioral therapy (CBT). This multi-site, randomized, controlled trial of a MBCT intervention will examine the value of this intervention in improving quality of life and decreasing depression in people with TBI. MBCT may represent a time-limited, cost-effective group intervention through which clinicians would have an opportunity to address some of the most debili- tating aspects of TBI. Study Purpose: The investigators will evaluate whether it is possible to PC-Based Cognitive Rehabilitation for improve memory and attention in patients who have suffered traumatic Traumatic Brain Injury brain injury through the use of at-home computer training. Patients will (TBI) be issued a computer and will train for three months on tasks that become more challenging as the subjects performance improves. The investigators will evaluate whether the training strengthened mental abilities in general, Department of but evaluating mental abilities in the laboratory before and after testing. Veterans Affairs Detailed Description: Here we propose two randomized clinical trials to PI: David L. Woods, Ph.D. determine if at-home PC-based adaptive training can improve cognitive function in chronic TBI patients. Both trials will use protocols designed to drive beneficial neuroplastic changes using paradigms similar to those that have shown promising results in smaller scale studies. The first experi- ment will investigate the effects of training of short-term verbal and spatial memory. Thirty-six patients with chronic mild, moderate and severe TBI will be evaluated with an extensive battery of neuropsychological tests (NPTs) and subjective rating scale measures at study entry. NPT and rating scale data will be compared to those obtained from 100 matched control subjects to characterize the cognitive deficits following mild, moderate and severe TBI. Patients will then be randomly assigned to immediate training (IT) or delayed training (DT) groups in a longitudinal crossover design. IT patients will begin training for 20 min/day on each of three different mem- ory tasks for a period of three months. Training data will be automatically uploaded to monitor daily compliance and learning rate. NPT and rating scale assessments will be obtained midway through the study. Compari- sons of changes in trained (IT) and untrained (DT) groups will be used to evaluate training efficacy. Then, during the second phase of the study, the DT group will undergo identical training. Repeat testing at the end of the study will quantify the effects of training on the DT group, and evaluate retention of training benefit in the IT group. The second experiment will evaluate the effects of training on attention and executive function using a similar randomized trial with a separate group of 36 chronic TBI patents. A comparison of the magnitude of training-related improvements in the two experiments will be used to evaluate specific and non-specific factors that contribute to training benefit and identify the patient characteristics that are most critical for successful cognitive rehabilitation.
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315 APPENDIX C Sample Description Study Type Study Design Time Frame N = 120 Interventional • Allocation: March 2009– Randomized April 2010 Gender: Both • Endpoint Classification: Group: Adult/Senior Efficacy Study • Intervention Model: Crossover Assignment • Masking: Open Label • Primary Purpose: Treatment N = 100 Interventional • Allocation: July 2009– Randomized December 2012 Gender: Both • Endpoint Classification: Group: Adult Efficacy Study • Intervention Model: Crossover Assignment • Masking: Open Label • Primary Purpose: Treatment
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316 COGNITIVE REHABILITATION THERAPY FOR TBI Study Title, Sponsor, and Principle Investigator Study Purpose and Detailed Description Study Purpose: Growth Hormone (GH) deficiency, defined by insufficient Recombinant Human Growth Hormone GH response to a variety of stimulating compounds, is found in 20-35% During Rehabilitation of adults who suffer traumatic brain injuries (TBIs) requiring inpatient re- From Traumatic Brain habilitation1. However, there is no accepted gold standard for diagnosing Injury GH deficiency in this population. Further, the major effector molecule of the somatotropic axis, Insulin-Like Growth Factor-1 (IGF-1) has recently been recognized as an important neurotrophic agent. Since most repair University of Texas and regeneration after TBI occurs within the first few months after injury, Southwestern Medical absolute or relative deficiencies of GH and IGF-1 in the subacute period Center; Baylor after TBI are potentially important factors why some patients fail to make University a good functional recovery. The proposed study is a randomized, double- PI: Ramon R. Diaz- blind, placebo-controlled trial of recombinant human Growth Hormone Arrastia, M.D., Ph.D. (rhGH), starting at 1 month post TBI, continuing for 6 months. This study has one primary hypothesis, that treatment with rhGH in the subacute period after TBI results in improved functional outcome 6 months after injury. As secondary hypotheses, we will investigate what is the optimal method to diagnose GH deficiency in TBI survivors and study the relation- ship between GH deficiency and insufficiency and functional recovery. Detailed Description: N/A Study Purpose: Context: Traumatic brain injury (TBI) is a common Rehabilitation of Trau- matic Brain Injury in condition associated with significant long-term cognitive, behavioral, Active Duty Military and functional morbidities. There are minimal controlled efficacy data Personnel and Veterans of various acute rehabilitation intervention approaches. Objective: To determine the relative efficacy of two different acute TBI rehabilitation approaches—cognitive-didactic versus functional-experiential. Second- The Defense and arily to determine relative efficacy for different patient subpopulations Veterans Brain Injury based on baseline cognitive functioning. Center; James A. Haley Veterans Detailed Description: A randomly assigned, intent-to-treat model of two Administration different comprehensive treatment programs conducted between July 19 Hospital; Hunter 1996 and May 16, 2003 in 360 adult participants with moderate to severe Holmes McGuire TBI treated in four participating Veterans Administration TBI rehabilitation Veteran Affairs centers. All patients admitted to the Commission for Accreditation of Re- Medical Center; habilitation Facilities (CARF) accredited acute inpatient rehabilitation brain Minneapolis injury programs at four participating Veterans Administration Medical Veterans Affairs Centers (VAMCs) (Minneapolis, Palo Alto, Richmond, and Tampa) during Medical Center; the study enrollment period were screened for eligibility. The design was a VA Palo Alto randomized-controlled trial with two treatment arms (cognitive-didactic Health Care System; and functional-experiential), both embedded within an interdisciplinary Department of TBI rehabilitation program. All treatment was hospital based. The interac- Veterans Affairs tive nature of the experimental conditions precluded subject blinding. Since PIs: Deborah L. each participating site serves a wide geographic area, the protocol permitted Warden, M.D., Elaine post-hospital outcome assessments by structured telephonic interview, to Date, M.D., Steven minimize drop out. Participants completed baseline assessment then received Scott, D.O., Barbara by random assignment one of the two standardized protocol rehabilitation Sigford, M.D., Ph.D., programs (summarized below and described in detail elsewhere). Partici- William Walker, M.D. pants received 1.5 to 2.5 hours daily of protocol-specific therapy plus an- other 2 to 2.5 hours daily of occupational and physical therapy. Independent teams of therapists functioned at each site to deliver the separate treatments and by necessity were not blinded to treatment. Protocol monitoring site visits, biweekly conference calls, and biannual investigator meetings were conducted to ensure uniformity of protocol treatment over time.
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317 APPENDIX C Sample Description Study Type Study Design Time Frame N = 164 Interventional • Allocation: September 2008– Randomized September 2012 Gender: Both • Control: Placebo Control Group: Adult • Endpoint Classification: Safety/Efficacy Study • Intervention Model: Parallel Assignment • Masking: Double • Blind (Subject, Caregiver, Investigator, Outcomes Assessor) • Primary Purpose: Treatment N = 360 Interventional • Allocation: July 1996–May Randomized 2003 Gender: Both • Intervention Model: Parallel Group: Adult/Senior Assignment • Masking: Single Blind (Outcomes Assessor) • Primary Purpose: Supportive Care
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318 COGNITIVE REHABILITATION THERAPY FOR TBI Study Title, Sponsor, and Principle Investigator Study Purpose and Detailed Description Study Purpose: Each year in the United States alone, a third of a mil- Resuscitative Endocrinology: Single- lion persons are hospitalized for traumatic brain injury (TBI), of whom Dose Clinical Uses for approximately one-quarter die. Most are less than 30 years of age. Estrogen-Traumatic Not only are the health care costs staggering for both initial care and Brain Injury rehabilitation, but the societal loss in terms of economic impact reaches into the billions of dollars annually in the United States alone. Despite advances in neurosurgical interventions and intensive care management, University of Texas many survivors do not fully recover. A significant cause of this mortality Southwestern Medical and morbidity is thought due to potentially preventable secondary injury, Center namely oxidant injury, inflammation, and apoptosis in the penumbra PI: Jane G. Wigginton, (the area of brain surrounding the primary lesion, which is at-risk, but M.D. potentially salvageable), beginning in the first few hours after the severe traumatic event. Despite the current bleak outlook for many of these patients, a series of animal investigations have uncovered a promising solution to the problem of the secondary injury seen in severe TBI and other similar processes, namely the early administration of estrogen, a strong anti-oxidant, anti-inflammatory and anti-apoptotic compound. Based on these encouraging results from animal studies, the investigators hypothesize that early administration of IV Premarin® in patients with severe TBI will safely reduce secondary brain injury, improve neurologi- cal outcomes, and improve survival. Detailed Description: N/A
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319 APPENDIX C Sample Description Study Type Study Design Time Frame N = 50 Interventional • Allocation: July 2009– Randomized Unknown Gender: Male • Control: Placebo Control Group: Adult • Endpoint Classification: Safety/Efficacy Study • Intervention Model: Parallel Assignment • Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) • Primary Purpose: Treatment
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320 COGNITIVE REHABILITATION THERAPY FOR TBI Study Title, Sponsor, and Principle Investigator Study Purpose and Detailed Description Study Purpose: The scientific objective of this program is to meet the Telerehabilitation for Operation Iraqi rehabilitation needs of combat wounded veterans with mild to moderate Freedom/ Traumatic Brain Injury (TBI) via telerehabilitation and determine the Operation Enduring effect of this modality of care on patients’ physical health and outcomes Freedom (OIF/OEF) including function and community participation. We will also evaluate Returnees with the benefits and limitations of rehabilitation using telehealth from the Combat-Related veteran and caregiver perspectives and evaluate the impact of rehabilita- Telerehab for Trau- tion via telehealth on Veterans Administration (VA) healthcare facility matic Brain Injury use. Detailed Description: Rational: TBI can cause life-long impairments in Department of physical, cognitive, behavioral and social function that are usually more Veterans Affairs disabling than the residual physical deficits. Recovery can continue many PI: Kris Siddharthan, years after initial trauma. Little is known about optimal methodologies Ph.D. to treat the vast and complicated secondary manifestations of combat- related TBI. Applicability: The goal of this rehabilitation program is eventually to optimally define telerehabilitation services for all veterans with polytrauma, including accurate and efficient screening instruments, educational material for patients and families, family support, and fam- ily counseling to enhance care coordination and to maximize functional outcomes and quality of life. Patient population: The program will help wounded veterans with a diagnosis of TBI from combat operations in Iraq and Afghanistan. Many veterans reside in rural and underserved areas. Although access to health care for rural patients remains a critical challenge, telerehabilitation may represent a viable means for the deliv- ery of therapeutic services to such patients, particularly those served by the VA. The program has implications for civilian populations as well including those injured in automobile or industrial accidents and similar in illness to the cohort of veterans we intend to follow. Clinical applica- tions, benefits and risks: The goals of the rehabilitation project will be to enhance the wounded veteran’s capacity to process and interpret in- formation and to improve his ability to function in all aspects of family and community life. It will involve a combination of restorative training which focuses on improving a specific cognitive function and compensa- tory training which educates veterans on adapting to the presence of a cognitive deficit that may or may not be curable using singular one to one interventions as well as integrated interdisciplinary approaches to target multiple conditions. We see no risks involved in this clinical inter- vention. Projected time to achieve a consumer-related outcome: The re- sults of the telerehabilitation project should immediately be available for dissemination throughout the VA. The VA has already committed itself to a nationwide rollout of similar telerehabilitation projects for wounded veterans. Hence, the findings should have immediate application in VA care for returnees from combat.
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321 APPENDIX C Sample Description Study Type Study Design Time Frame N = 85 Interventional • Control: July 2008–May Uncontrolled 2012 Gender: Both • Endpoint Classification: Group: Adult Efficacy Study • Intervention Model: Single Group Assignment • Masking: Open Label • Primary Purpose: Treatment
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322 COGNITIVE REHABILITATION THERAPY FOR TBI Study Title, Sponsor, and Principle Investigator Study Purpose and Detailed Description Study Purpose: The objective of this trial is to evaluate the effectiveness of The Study of Cogni- tive Rehabilitation cognitive rehabilitation in OIF/OEF service members with a history of mild Effectiveness for Mild traumatic brain injury and persistent (3–24 months post-injury) cognitive Traumatic Brain Injury complaints. This is a prospective, randomized, control treatment trial of (SCORE) cognitive rehabilitation for OEF/OIF Service Members with a history of mild traumatic brain injury and persistent (3–24 months post-injury) cogni- tive complaints. Subjects will be recruited from consecutive patient referrals Brooke Army Medical to the TBI Service at SAMMC-North. Patients who meet eligibility criteria Center; The Defense and consent to participate in the treatment trial will be randomly assigned and Veterans Brain In- to one of four, 6-week treatment arms of the study. Subjects will be evalu- jury Center; Henry M. ated prior to the start of treatment and 3, 6, 12, and 18 weeks following Jackson Foundation the initiation of the study. The total number of patients to be studied is 160 for the Advancement (maximum), which is approximately 20 patients per month. of Military Medicine Detailed Description: PI: Douglas B. Cooper, Ph.D. This is a prospective, randomized, control treatment trial of cognitive reha- bilitation for OEF/OIF Service Members with a history of mild traumatic brain injury (mTBI) and persistent (3–24 months post-injury) cognitive complaints. Subjects will be recruited from consecutive patient referrals to the TBI Service at SAMMC-North. Patients who meet eligibility criteria and consent to participate in the treatment trial will be randomly assigned to one of four, 6-week treatment arms of the study: 1. Psychoeducational control group; 2. Non-therapist directed, computerized cognitive reha- bilitation; 3. Therapist-directed individualized cognitive rehabilitation; and 4. Integrated interdisciplinary cognitive rehabilitation combined with cognitive-behavioral psychotherapy. (Components of the treatment arms are described in detail in section 4.6; Research Design and Methods.) All subjects enrolled in the study will receive the standard of care in manage- ment of chronic post-concussive symptoms, consistent with the VA/DoD Clinical Practice Guidelines for the Management of Concussion/mild TBI (Barth et al., 2009), regardless of treatment assignment. The standard of care includes provision of patient education materials (adapted from exist- ing studies to address more persistent rather than acute symptom manage- ment), regular scheduled follow-up with a medical provider every 3 weeks, and symptom-based treatment of post-concussive complaints (e.g., medica- tion trials for headache and co-occurring psychiatric disorders, physical therapy for vestibular complaints, case management, and supportive coun- seling with social work for soldiers assigned to the Warriors-in-Transition Battalion). Study participants who are assigned to treatment arms 2, 3, or 4 will additionally receive manualized cognitive rehabilitation therapies during the 6-week treatment phase of the study. Cognitive rehabilitation treatment intensity (i.e., number of hours of treatment per week) will be matched for individuals assigned to treatment arms 2, 3, or 4. Participants assigned to the control treatment group (treatment arm 1) will be offered individualized cognitive rehabilitation therapy if their cognitive complaints do not abate following the completion of the 6-week treatment trial. Study participants will be evaluated prior to the initiation of treatment, as well as at 3-weeks, 6-weeks, 12-weeks, and 18-weeks following the start of treat- ment. Study evaluators will be blind to treatment assignment. Pre-treatment baseline assessments and peri-/post-treatment outcome assessments will include demographic information, injury-related variables, self-report inven- tories, performance on neuropsychological testing, and functional status (e.g., work status; healthcare utilization). Detailed descriptions of the data to be collected including primary and secondary outcome measures, as well as co- variate measures can be found in section 4.8: Instrumentation.
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323 APPENDIX C Sample Description Study Type Study Design Time Frame N = 160 Interventional • Allocation: Randomized June 2011– • Endpoint Classification: August 2014 Gender: Both Efficacy Study • Intervention Model: Group: Adult Factorial Assignment • Masking: Double Blind (Subject, Outcomes Assessor) • Primary Purpose: Treatment
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