Amantadine + rTMS as a Neurotherapeutic for Disordered Consciousness
Condition: Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic
Study type: Interventional

Summary: 
      The purpose of this study is to examine the safety and efficacy of repetitive transcranial
      magnetic stimulation (rTMS) combined with Amantadine relative to rTMS Alone and Amantadine
      Alone for persons in chronic states of seriously impaired consciousness. The hypothesis is
      that provision of rTMS+Amantadine will provide a safe yet synergistic effect that induces or
      accelerates functional recovery.
    

Detailed description: 
      The R21 research objective is to examine the safety and efficacy of repetitive transcranial
      magnetic stimulation (rTMS) combined with Amantadine (TMS + Amantadine) relative to rTMS
      Alone and Amantadine Alone for persons in chronic states of seriously impaired consciousness.
      The hypothesis is that provision of rTMS+Amantadine will provide a safe yet synergistic
      effect that induces or accelerates functional recovery. This hypothesis is based on (a)
      preliminary data indicating partially improved neurobehavioral functioning mechanistically
      related to rTMS-induced neural activity and connectivity as well as improved integrity of
      white fiber tracts, (b) relationship between dopamine (DA) and common traumatic brain injury
      (TBI) impairments, (c) role of DA in mediating consciousness, (d) the commonality between and
      DA and rTMS-targeted pathways, (e) clinical efficacy and safety of Amantadine, (f) mechanisms
      of action of Amantadine, and (g) the association between rTMS and Amantadine with
      up-regulating brain derived neurotrophic factor. The rationale is that pairing rTMS with
      Amantadine will have a complementary and synergistic effect on factors promoting conscious
      behavior. The specific aims are to: (1) Demonstrate that rTMS+Amantadine is safely tolerated,
      (2) Determine neurobehavioral effect of rTMS+Amantadine, and (3) Characterize pre-and
      post-treatment neural changes in neural activation. Aim 1 is based on our preliminary safety
      data and safety data regarding Amantadine. To address Aims 2 & 3 we use a repeated measures
      baseline control design with randomized treatment orders yielding three treatment groups;
      rTMS + Amantadine, rTMS Alone and Amantadine Alone. Analyses for Aims 2 and 3 involve
      comparing these treatment groups according to neurobehavioral growth trajectories, mean
      amount of neural activation and connectivity within and between brain regions, and indices of
      fiber tract directionality.
    

Intervention name(s): rTMS; Amantadine
Intervention type(s): Device; Drug
Other intervention name(s): Repetitive Transcranial Magnetic Stimulation; Symadine; Symmetrel
Intervention MeSH terms: Amantadine
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Traumatic Brain Injury; Transcranial Magnetic Stimulation; Amantadine; Vegetative State; Minimally Conscious State