Efficacy of Repetitive Transcranial Magnetic Stimulation for Improvement of Memory in Older Adults With TBI
Condition: Brain Injuries, Traumatic; Repetitive Transcranial Magnetic Stimulation; Memory Deficits; Aging
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Memory Disorders
Study type: Interventional

Summary: 
      The proposed study will evaluate the safety, durability and efficacy of repetitive
      Transcranial Magnetic Stimulation (rTMS) as a promising non-invasive therapeutic treatment
      for improving memory in older adults with mild or moderate Traumatic Brain Injury (TBI) who
      have been experiencing residual memory or cognitive problems that affect daily functioning.
    

Detailed description: 
      Recent advances in both AD and TBI test non-pharmaceutical interventions that target chronic
      symptom improvement (e.g., non- invasive brain stimulation, exercise and cognitive training).
      In order to provide targeted therapies to patients who suffer from chronic sequela of TBI it
      is necessary to understand mechanisms of repair within the context of an aging brain.
      Repetitive TMS (rTMS) delivers therapeutic, noninvasive brain stimulation, is FDA-approved
      for treatment for major depression and currently used for treatment of pain, PTSD, anxiety,
      improvement of executive function in mild and moderate TBI, severe TBI, memory enhancement
      and dementia.

      This treatment can induce neuronal long-term potentiation resulting in synaptic repair
      leading to improvements in memory function through hippocampal- cortical circuits and brain
      connectivity measured by resting state-fMRI (rs fMRI) particularly in default mode and
      central executive network (DMN & CEN). The study primarily proposes to assess the efficacy of
      rTMS to improve memory performance and to test rs-fMRI (i.e. DMN) as a potential biomarker to
      capture response to treatment in older patients suffering with chronic symptoms related to
      previous brain injuries (depression, PTSD etc). In addition, the study will assess other
      established biomarkers longitudinally (e.g.,hypometabolism via PET FDG, cortical oscillation
      via electroencephalography (EEG), Brain Derived Nerve Growth Factor (BDNF)and hippocampal
      volume from structural MRI) to capture patient response to treatment that may signal early
      dementia.

      HYPOTHESES:

      Primary:

      Subjects with TBI who receive active rTMS treatment (rTMS_A) will: a) show significantly
      greater improvement from baseline in memory performance post rTMS intervention compared to
      subjects who received sham rTMS treatment (rTMS_S), and b) show stronger functional
      connectivity within and between DMN and CEN post rTMS intervention compared to patients who
      received sham (rTMS_S).

      Secondary:

        1. Quality of Life (QOL): scores on QOL scale will improve with rTMS treatment in patients
           who receive rTMS treatment.

        2. Sustained Improvement: At 6-month follow-up, patients with TBI in rTMS_A group would be
           more likely to have sustained greater brain connectivity compared to patients in the
           rTMS_S group predicting better memory performance.

        3. Moderators of Response: The following variables may moderate memory function improvement
           in patients with TBI post intervention and at 6-month follow-up: Age, health condition
           variables (severity of symptoms at baseline, time to injury, baseline cognitive
           performance, TBI type,comorbidities (PTSD, sleep, depression), substance abuse,
           medication use, fatigue); physiological and biological variables (baseline hippocampal
           volume and/or microstructure, baseline connectivity in DMN & CEN, EEG resting and
           task-related cortical oscillations, and Brain Derived Neurotrophic Factor (BDNF)
           genotype.

        4. Mediators of Response: To assess the mechanism of rTMS in synaptic repair/regeneration,
           pre and post changes will be assessed in depression and PTSD measures, Plasma BDNF, FDG
           PET hypometabolism in precuneus/posterior cingulate area, EEG resting and task-related
           cortical oscillations, and connectivity of DLPFC (stimulation site & part of CEN) with
           other DMN.

      SPECIFIC OBJECTIVES:

      Primary Objective: a) To assess the efficacy of rTMS to predict improvement in memory
      performance pre and post rTMS intervention in older patients with TBI, and b) To assess
      rs-fMRI as a biomarker to detect these changes in memory performance.

      Secondary Objective: To assess the mechanism of rTMS in synaptic repair/regeneration by
      assessment of structure & functional brain activity (PET/MRI, fMRI, & EEG), genetic,
      cognitive and behavioral function factors (including QOL, depression and PTSD).
    

Intervention name(s): Repetitive Transcranial magnetic Stimulation
Intervention type(s): Device
Intervention description(s): RTMS will be delivered via magventure machine, on an approved FDA IDE protocol to DLPFC region to improve memory in older adults (veterans and non-veterans) with mild and moderate TBI.
Other intervention name(s): rTMS
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The proposed study will evaluate the safety, durability and efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) as a promising non-invasive therapeutic treatment for improving memory in older adults with mild or moderate Traumatic Brain Injury (TBI) who have been experiencing residual memory or cognitive problems that affect daily functioning.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: repetitive Transcranial Magnetic Stimulation; Brain Injuries, Traumatic