Traumatic Brain Injury in Veterans and Near-Infrared Phototherapy
Condition: TBI (Traumatic Brain Injury)
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Wounds and Injuries
Study type: Interventional

Summary: 
      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).
    

Detailed description: 
      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.
    

Intervention name(s): Near-Infrared Phototherapy
Intervention type(s): Device
Intervention description(s): The In Light Wellness Systems Near-Infrared Phototherapy Device (manufactured by In Light Wellness Systems, Inc.) contains alternating rows of 402 red (640 nm) and infrared (880 nm) light-emitting diodes embedded in 2 neoprene pads. One pad circles the skull, providing 720 Joules/min, and the other pad covers the top of the head, providing 360 joules/min. For each treatment session, the "A" setting on the 3-port controller is utilized, which runs approximately 6.7 min of 73 Hz, 587 Hz, and 1175 Hz in an automated sequential manner. No other interventions were utilized.
Other intervention name(s): Polychromatic Light Therapy
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment