rTMS to Improve Cognitive Function in TBI
Condition: Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic
Study type: Interventional

Summary: 
      This project will study 40 Veterans identified with symptoms understood to characterize mild
      to moderate Traumatic Brain Injury (TBI) including Post Traumatic Stress Disorder (PTSD).
      Following screening and informed consent, Veterans will be randomly assigned to treatment
      with repetitive Transcranial Magnetic Stimulation (rTMS) or sham rTMS (placebo). Additional
      examinations will compare brain imaging (structural and functional MRI scans at rest) across
      participants at baseline, after acute rTMS treatment, and at 6 month followup. The VA
      population differs significantly from populations that have been included in prior trials of
      rTMS for many conditions such as depression, chronic pain, and PTSD. Many returning Operation
      Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) personnel and Veterans with concussion
      histories report cognitive problems, such as impaired attention, verbal fluency, poor
      planning, reduced working memory, and mental flexibility. The investigators hope to show the
      efficacy and durability of rTMS in treating these symptoms safely in Veterans with
      co-morbidities.
    

Detailed description: 
      The goal of the present study is to evaluate the efficacy and durability of benefits of
      repetitive Transcranial Magnetic Stimulation (rTMS) as a promising non-invasive therapeutic
      treatment for executive function deficits reported in Veterans with mild to moderate
      Traumatic Brain Injury (TBI) patients. Although much progress has been made towards
      understanding the various deficits following TBI, progress has yet to be made towards
      identifying and assessing therapeutic treatment options that are responsive to TBI symptoms.
      Many returning OEF/OIF Veterans with concussion histories report cognitive symptoms that may
      last for months or years, and affect every day function. Symptoms faced by Veterans with mild
      to moderate TBI include executive function deficits such as impaired attention (including
      shifting sets), verbal fluency, poor planning, reduced working memory, and mental
      flexibility. The primary objective is to assess the efficacy of rTMS in Veterans with mild to
      moderate TBI in improving executive functioning.

      A recent VA study reported improvements in PTSD and related symptoms in Veterans with PTSD
      who received rTMS (Watts et al., 2012). Repetitive TMS is a method of delivering therapeutic,
      non-invasive brain stimulation that is currently being used at the VA Palo Alto and Stanford
      University in a number of clinical trials.

      For this pilot study the investigators propose to enroll 40 Veterans diagnosed with mild to
      moderate TBI (age range 20-65). Inclusion Criteria: mild and moderate TBI will be defined as:
      post-traumatic amnesia (PTA < 1 day for mild; 1 day> x < 7days for moderate). Because of the
      extensively documented co-occurrence of TBI with PTSD, (Veterans with TBI with and without
      PTSD will be enrolled). PTSD will be assessed using standard clinical measures. Exclusionary
      criteria: patients will be screened for TMS and MRI safety. The duration of the study will be
      two years, with a 1.5 year enrollment period, and a final half-year of follow-up completion.
      Following a preliminary telephone screen, Veterans will be scheduled for onsite informed
      consent, screening, and baseline assessments. Using an electronic randomization form,
      participants will be enrolled into two groups: active rTMS or sham rTMS. As this is a double
      blind placebo controlled study, only the subject ID number is provided to the nurse
      administrating the rTMS treatment. After randomization, the rTMS nurse will test the motor
      threshold (MT) for rTMS. Each participant will be in the trial for a total of approximately
      (28) weeks: 1-2 weeks screening, (2) weeks acute treatment phase (including MRI pre and post
      rTMS) and 24 weeks (6 month) follow-up phase (with MRI, neuropsychological testing and
      self-report measures). Left Dorsolateral Prefrontal Cortex (DLPFC) will be the stimulation
      site as it is shown to be affective in treatment of depression and approved by FDA. All
      participants will receive a minimum of 20 treatments before being evaluated for change in
      executive function (primary outcome measure).

      The primary hypothesis is that Veterans receiving active rTMS will show improvement more than
      sham treated Veterans in (performance between baseline and last assessment of >1 SD on either
      the Trail Making Test part B, Delis-Kaplan Executive Function System [D-KEFS] Verbal Fluency
      and/or D-KEFS Color-Word Interference Test). Additional analysis will include: Sustained
      Improvement on executive function composite score; secondary consequences of TBI scores on
      Quality of Life (QOL) scale, moderators of response such as age, severity of symptoms at
      baseline, type of comorbidity (e.g., PTSD); and, functional brain activity changes with rTMS
      treatment. This pilot study will be one of the first to demonstrate rTMS as a treatment for
      executive function deficit in Veterans with mild to moderate TBI. Additionally, it would also
      report on the efficacy of using functional MRI (fMRI) as a biomarker to capture this
      improvement in executive function.
    

Intervention name(s): rTMS; Sham rTMS
Intervention type(s): Device; Device
Intervention description(s): Repetitive Transcranial Magnetic Stimulation; Placebo Device that simulates active rTMS treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: TBI; Transcranial Magnetic Stimulation, Repetitive; magnetic resonance imaging functional; Quality of life; Executive Function; Veterans