What’s New in Traumatic Brain Injury Clinical Trials?

Eric Robinson, Ross University School of Medicine

Traumatic brain injuries (TBI) are a major public health concern in the United States. Each year, TBIs contribute significantly to morbidity and mortality, with the Centers for Disease Control and Prevention (CDC) estimating 64,000 TBI-related deaths in the United States in 2020 alone¹. The long-term consequences of traumatic brain injuries can be further debilitating, resulting in a significant impact on families and caregivers. The Brain Injury Association of America estimates that there are 5.3 million individuals in the United States living with brain injury-related disability². Clinical trials play an integral role in the discovery of new approaches to treating and improving recovery from traumatic brain injury, in an attempt to alleviate the burden of traumatic brain injuries on society and improve the quality of life for patients.

It is beneficial to researchers and clinicians alike to have an understanding of the current state of clinical trials. ClinicalTrials.gov is a publicly accessible online registry of clinical research studies that are conducted worldwide. It is maintained by the US National Library of Medicine at the National Institutes of Health, with the purpose of providing information about clinical studies to the public. To gain some insight into the current state of clinical trials, I searched the ClinicalTrials.gov registry for key terms, and organized the results according to reported categories.

A search of the ClinicalTrials.gov database for clinical trials related to “Brain Injuries, Traumatic” produces 1,934 such trials, as of August 5, 2023³. The search key used in the search included synonyms for brain (cerebral, human brain, brain structure), brain injuries (brain injury, brain damage, acquired brain injury, injury brain, cerebral damage), brain injuries traumatic (traumatic brain injury, brain trauma, traumatic brain injuries, traumatic encephalopathy, brain injury traumatic, traumatic brain damage, traumatic encephalopathies), injuries (trauma, injury, traumatic injury, wound). Among the resulting trials, 74 are active, not recruiting, and 879 trials are listed as completed (Table 1). Among the 74 active clinical trials, 55 are interventional and 19 are observational. Of these active trials, one is in Early Phase 1 trial, two are in Phase I, two are in Phase I/Phase II, three are in Phase II, two are in Phase II/Phase III and two are in Phase III; 62 were labeled “blank” or “not applicable.” Of the total 1,934 clinical trials, 28 are listed early Phase I, 87 are in Phase I, 201 are in Phase II, 111 are in Phase III, 73 are in Phase IV and 906 are listed as not applicable. Additionally, 528 trials do not list a phase.

Table 1. Status of Clinical Trials Related to “Brain Injuries,Traumatic”

The clinical trials related to “Brain Injuries,Traumatic” investigate a total of 1,027 conditions, with traumatic brain injury (398), brain injuries, traumatic (56), mild traumatic brain injury (53), chronic subdural hematoma (37) and brain injuries (30) are the most commonly studied conditions.

The funding sources for these trials were varied. Of the 1,934 trials, 185 list funding from industry sources, 177 from U.S. federal sources, 43 from the National Institutes of Health (NIH), 5 list individual, 4 list a network and 1,479 list funding from other sources; with 37 from other governmental funding. The top five federal funding agencies of clinical trials related to traumatic brain injuries, excluding NIH are the VA Office of Research and Development (74), VA Eastern Colorado Health Care System (13) The US Department of Veterans Affairs (12), Uniformed Services University of Health Sciences (11) and Walter Reed National Military Medical Center (7).

Within the NIH funding source, the top agencies funding the most clinical trials include National Institute of Neurological Disorders and Stroke (NINDS) (14), National Institutes of Health Clinical Center (CC) (11), National Institute of Mental Health (NIMH) (7), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (5) and National Institute of Nursing Research (NINR) (5). Several industry groups, pharmaceutical companies and medical centers are also involved in funding clinical trials related to traumatic brain injuries. Banyan Biomarkers (9), BrainScope Company (9), ElMindA (9), Helius Medical (6) and Ipsen (6) are some of the most frequently cited industry funding sources. The of the most frequently cited “other” funding sources include the Kessler Foundation (38), University of Washington (31), Children’s Hospital Medical Center, Cincinnati (24), University of Pittsburgh (21) and Assistance Publique–Hôpitaux de Paris (18).

Clinical trials on traumatic brain injuries explore a wide range of interventions. The most commonly listed interventions include: behavioral (365), drug (365), device (336), other (322), procedure (119), diagnostic test (63), dietary supplement (30), biological (28), radiation (12), combination product (6), genetic (2), with 286 omitting an intervention type (Figure 1). The most commonly studied behavioral interventions among clinical trials include Acceptance and Commitment Therapy (ACT) (2), Art Therapy (2), and Collaborative Care (2). The most commonly studied devices include Transcranial Direct Current Stimulation (7), Portable Neuromodulation Stimulator (PoNS) treatment (5) and repetitive transcranial magnetic stimulation (4). The most commonly investigated diagnostic tests include Dynamic Vision Testing (Bertec Vision Advantage System) and Balance Error Scoring System (2), sample collection (2) and transcranial doppler (2). The most common procedures being investigated include acupuncture (3), decompressive craniectomy (3) and embolization of middle meningeal artery (3).

Figure 1. Categories of Interventions in Clinical Trials Related to “Brain Injuries,Traumatic”

Based on a search of clinical trials related to traumatic brain injuries, it is apparent that this area of research continues to be an exciting and active. There is a large number of clinical trials that have already been completed, as well as numerous active studies and studies currently recruiting participants that may provide interesting results. These studies investigate a diverse range of treatments and interventions for patients suffering from brain injuries. While there have been nearly a thousand clinical trials related to traumatic brain injuries completed, there is a still a strong need for active research. It is hopeful that while there are only 74 currently active trails, there are a significant number (351) currently recruiting. Clearly, there is an ongoing need for the investment of resources into clinical trials for traumatic brain injuries.

References:

1. National Center for Health Statistics Mortality Data on CDC WONDER [Internet]. Centers for Disease Control and Prevention; 2023 Jan. Available from: https://wonder.cdc.gov/mcd.html
2. Report to Congress: Traumatic Brain Injury in the United States [Internet]. National Center for Injury Prevention and Control; 1999 Dec. Available from: https://www.cdc.gov/traumaticbraininjury/pubs/tbi_report_to_congress.html
3. Targeted search for the condition “Brain Injuries,Traumatic” on ClinicalTrials.gov: “Brain Injuries,Traumatic”