TBI (Traumatic Brain Injury) Clinical Trial
Official title:
Treatment of Mild and Moderate Traumatic Brain Injury in Veterans Using Near-Infrared Phototherapy
This is a proof-of-concept study designed to demonstrate whether increases in cerebral blood flow, improvements in brain functioning, and reductions in symptomology associated with traumatic brain injury (TBI) can result from treatments consisting of near-infrared phototherapy (NIR).
The incidence of traumatic brain injury is widespread. The Centers for Disease Control
estimate that 1.7 million TBIs occur each year and that TBI is a contributing factor in
about 30% of all injury-related deaths. In addition, about 75% of these TBIs are
concussions, or mild TBIs (mTBI). However, such concussions, especially multiple concussions
that occur over time, are not harmless. The damage of even mild TBI can potentially lead to
neuropsychiatric sequelae. Moreover, injury to the brain can worsen over time depending on
the degree of inflammatory response and the areas of injury. TBI induces a number of
neuropathological changes like aggregation of beta amyloid and tau proteins along with
neuroinflammatory changes that resemble the pathology of degenerative diseases.
For many of our returning Veterans, improvised explosive devices (IEDs) have been the cause
of these TBIs. For example, data from the Defense Manpower Data Center indicates that as of
October 3, 2011, explosive devices have been responsible for an estimated two-thirds or more
of the battlefield injuries in Iraq; of the 46,532 warriors wounded in Operations Enduring
Freedom and Iraqi Freedom, 30,347 were wounded by explosive devices, many of which were
IEDs. Most of these injuries involved concussive brain injury. While current estimates are
that 15-19% of all returning Warfighters have a history of acute concussion or TBI during
their tour(s) of duty. It has been noted that "22.8% of a Brigade Combat Team returned from
Iraq with confirmed deployment-acquired traumatic brain injury."
Currently, there are no effective treatments for reversing or reducing the brain damage
following TBI. Confounding the situation further, the symptoms of TBI can often overlap with
those of post-traumatic stress disorder (PTSD) such as headache, dizziness, irritability,
memory impairment, delayed problem solving, slowed reaction time, fatigue, visual
disturbances, sleep disturbances, sensitivity to light and noise, impulsivity, judgment
problems, emotional outbursts, depression, and anxiety. In addition, the rates of
depression, anxiety, and other psychological symptoms are markedly elevated in TBI
survivors, based on studies involving large samples of patients. As a result of this
complexity and overlap of symptoms between TBI, PTSD, and depression, a clear diagnosis of
TBI can be challenging, which can lead to misdirected treatment efforts and hamper the
ability to accurately assess treatment response.
Multiple published research studies have validated the healing mechanisms of NIR, which can
be delivered via light-emitting diodes (LED). NIR phototherapy has been used extensively for
wound healing of soft tissue, for increasing circulation, for the treatment of pain and for
specific conditions such as hair growth and carpal tunnel syndrome.
The mechanism of action that is central to the healing effect of NIR is increased blood
circulation via the release of nitric oxide from red blood cells. Local increases in nitric
oxide increase blood flow through arteries, veins and lymphatic ducts. Increased return of
flow from treated sites helps to diminish intracellular acidosis that could alter
mitochondrial membrane potential(s). This hypothesis holds that when blood flow is adequate,
it provides a sufficient amount of oxygen and glucose to cells for adenosine triphosphate
(ATP) generation by mitochondria. However, even a modest decrease in regional or global
blood flow in the brain, such as that seen in TBI, will limit the amount of glucose and
oxygen delivered to neurons. Restoring blood flow levels in damaged regions of the brain
thus restores the necessary levels of glucose and oxygen required for ATP generation and
proper neuronal functioning.
In addition, nitric oxide stimulates angiogenesis and increased numbers of capillaries will
aid in increasing blood flow (and oxygen and glucose) in injured areas of the brain where
blood flow was subnormal. This effect contributes to enhanced mitochondrial function. The
1998 Nobel Prize for physiology was awarded to Furchgott, Ignarroand, and Murad for their
discovery that nitric oxide acts as a signaling molecule and activates an enzyme, guanylate
cyclase (GC), which is necessary for subsequent vasodilation.
Finally, nitric oxide is an effective analgesic; it appears to reduce pain either by
reversing local ischemia or directly in a manner akin to the analgesic effect of morphine.
In the latter case, nitric oxide helps to regulate membrane potential via alterations in the
activity of the ATP dependent potassium channel. This effect may be mediated by activated GC
and subsequent phosphorylation of the potassium channel.
Due to its capacity to non-invasively penetrate the skull, NIR has been safely used since
the late 1970s for the determination of cerebral blood flow and oxygen levels in brain
injured adults, post-stroke patients, and in pediatric patients. Furthermore, transcranial
NIR has been shown to increase cortical perfusion and is associated with clinical
improvement in human subjects with traumatic brain injury, neurodegenerative disease, and
depression. The NIR device for this study is FDA cleared (510K; K101894) for increasing
circulation and reducing pain.
;
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT04526639 -
VR Cognitive Rehabiliation for Pediatric TBI
|
N/A | |
Recruiting |
NCT05943756 -
Evaluation of Well-being Interventions in Adults With TBI
|
N/A | |
Completed |
NCT01339702 -
The EPIC Project: Impact of Implementing the EMS Traumatic Brain Injury Treatment Guidelines
|
||
Completed |
NCT00760734 -
Hyperbaric Oxygen Therapy (HBOT) in Chronic Traumatic Brain Injury (TBI)/Post Concussion Syndrome (PCS) and TBI/Post-Traumatic Stress Disorder (PTSD)
|
Phase 1 | |
Not yet recruiting |
NCT06024122 -
Brain Development in Young Children Following Mild Traumatic Brain Injury - Pilot Study
|
||
Completed |
NCT03896789 -
Pediatric Guideline Adherence and Outcomes- Argentina
|
N/A | |
Completed |
NCT03225768 -
Guided Training for People With Cognitive Impairment
|
N/A | |
Completed |
NCT04590911 -
Effectiveness of Multimodal Cognitive Rehabilitation for Traumatic Brain Injury Sustained During Older Adulthood
|
N/A | |
Recruiting |
NCT04121780 -
Growth Hormone Replacement Therapy for Retried Professional Football Players
|
Phase 2 | |
Completed |
NCT04776304 -
Art Therapy qEEG Study for Service Members With a Traumatic Brain Injury and Posttraumatic Stress Symptoms
|
N/A | |
Completed |
NCT00409058 -
Teen Online Problem Solving (TOPS) - An Online Intervention Following TBI
|
N/A | |
Completed |
NCT00205491 -
Pharmacological Intervention in Depression After Traumatic Brain Injury
|
Phase 4 | |
Completed |
NCT03490110 -
Brain Markers of Improvements in Cognitive Functioning
|
N/A | |
Active, not recruiting |
NCT02525432 -
Autologous Stem Cell Study for Adult TBI (Phase 2b)
|
Phase 2 | |
Completed |
NCT02858544 -
Concussion in Motor Vehicle Accidents: The Concussion Identification Index
|
N/A | |
Completed |
NCT01728831 -
Study of Cerebral Tissue Oxygenation During Transfusion in Traumatic Brain Injury
|
N/A | |
Recruiting |
NCT06005194 -
InMotion - Telehealth Delivered Exercise Promotion to Treat Major Depression After TBI
|
N/A | |
Not yet recruiting |
NCT05340803 -
Sedation of Ventilated Traumatic Brain Injury Patients With Midazolam Alone Versus Combination With Dexmedetomidine or Magnesium Sulfate; Monitored by Ultrasonograghic Optic Nerve Sheath Diameter
|
Phase 3 | |
Recruiting |
NCT06195345 -
Individual Cerebral Hemodynamic Oxygenation Relationships (ICHOR 1)
|
||
Recruiting |
NCT04279431 -
Follow-up of mTBI Patients Discharged From the ED Using Standard Clinical Triage Including BrainScope One
|