rTMS to Improve Cognitive Function in TBI (rTMSTBI)
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|ClinicalTrials.gov Identifier: NCT02152540|
Recruitment Status : Completed
First Posted : June 2, 2014
Results First Posted : May 7, 2019
Last Update Posted : August 14, 2019
|Condition or disease||Intervention/treatment||Phase|
|Traumatic Brain Injury||Device: rTMS Device: Sham rTMS||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||33 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Outcomes Assessor)|
|Official Title:||Repetitive Transcranial Magnetic Stimulation to Improve Cognitive Function in TBI|
|Actual Study Start Date :||October 1, 2014|
|Actual Primary Completion Date :||September 30, 2017|
|Actual Study Completion Date :||June 30, 2019|
Experimental: ACTIVE rTMS
Those receiving experimental treatment will receive 20 sessions of rTMS. The treatment will be delivered by trained medical personnel.
Repetitive Transcranial Magnetic Stimulation
Placebo Comparator: Sham rTMS
Those receiving the sham rTMS will receive 20 sessions of sham rTMS. The treatment will be delivered by trained medical personnel.
Device: Sham rTMS
Placebo Device that simulates active rTMS treatment
- Trail Making Test Part B [ Time Frame: Baseline (up to two weeks after screening visit); Post-Treatment (2 weeks from end of Baseline up to one month from entering the study but always the day of last treatment) ]
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 the Trail Making Test part B. This test is known for its accurate assessment of executive function in mild and moderate TBI.
The TMT is a timed test and the goal is to complete the test as accurately and as quickly as possible. Raw scores are reported in seconds to complete the test. For Part B, an average score is 75 seconds and a deficient score is greater than 273 seconds.
The present study reports T-scores, which can range from a minimum of 0 and a maximum of 100. The higher the T- score achieved by a participant, the better the performance, indicating a higher level of functioning.
- Sustained Improvement on Executive Function [ Time Frame: 6-month post treatment follow up ]At the end of the 6 month post treatment followup TBI patients who received rTMS would be more likely to continue to have greater "executive function improvement" on Trail making test part B than patients who received Sham rTMS.
- Quality of Life (QOL) Scale [ Time Frame: One month ]The Veterans RAND 36 Item Health Survey (VR-36©) is a brief, generic, multi-use, self-administered health surveys comprised of 36 items The instruments are primarily used to measure health-related quality of life, to estimate disease burden and to evaluate disease-specific impact on general and selected populations. The items on the questionnaire correspond to eight principal health domains including general health perceptions, physical functioning, role limitations due to physical and emotional problems, bodily pain, energy-fatigue , social functioning and mental health. higher scores mean better health and depicted in percentages. This scale would show significantly greater improvement in patients with mild to moderate TBI who received rTMS treatment.
- Moderators of Response [ Time Frame: one month ]Moderators of response such as age, severity of symptoms at baseline, time to injury, type of comorbidity, PTSD, sleep depression, substance abuse, medication use, cognitive exercises, fatigue, TBI type, duration of illness, prior treatment resistance (rTMS/ECT) or any combination of these, may affect or moderate the treatment response.
- Functional Brain Connectivity [ Time Frame: Six month follow-up ]Greater functional connectivity will be observed in hub centers of the Default Mode Network (DMN), particularly the precuneus/posterior cingulate area as measured by resting state fMRI/diffusion tensor imaging (DTI) at follow up compared to baseline in those TBI patients treated with rTMS compared to those treated with sham.
- Mediators of Response [ Time Frame: 6 month follow up ]Mediators of response to treatment: to establish a preliminary understanding of the underlying mechanisms related to rTMS modulation of synaptic repair in TBI we will also look at brain-derived neurotrophic factor (BDNF) samples in our population.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02152540
|United States, California|
|VA Palo Alto Health Care System, Palo Alto, CA|
|Palo Alto, California, United States, 94304-1290|
|Principal Investigator:||Maheen M Adamson, PhD||VA Palo Alto Health Care System, Palo Alto, CA|