An interventional study of Repetitive Transcranial magnetic Stimulation in Brain Injuries, Traumatic, Repetitive Transcranial Magnetic Stimulation and Memory Deficits, sponsored by Palo Alto Veterans Institute for Research. Completed at 1 site in United States. Open to participants aged 50 Years to 75 Years. Per ClinicalTrials.gov, last updated 2023-04-11.
Sponsored by Palo Alto Veterans Institute for Research · Not applicable, Interventional, and Treatment
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.
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:
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).
2,113 studies on the registry are indexed under Brain Injuries; 385 are open to participants now.
This study's enrollment of 33 is below the median of 48 across 1,331 interventional studies indexed under Brain Injuries.
Browse Brain Injuries studies →Palo Alto Veterans Institute for Research is the lead sponsor of 51 studies on the registry; 10 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Patients with mild and moderate TBI will be assigned randomly to this arm and will not receive treatment
Patients with mild and moderate TBI will be assigned randomly to this arm and will receive treatment
Device: Repetitive Transcranial magnetic Stimulation
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.
Also known as: rTMS
CANTAB Paired Associates Learning (PAL)
Test for visual memory and new learning: it is a hippocampal-mediated paired associates learning task. This test has twenty-one outcome measures, covering the errors made by the participant, the number of trials required to locate the pattern(s) correctly, memory scores and stages completed (Administration time 10 minutes). The main score provided is the sum of pairs reproduced over three trials (range: 0-30). We will use the average number of trials needed to succeed on PAL task as the main outcome measure.
Time frame: 2-4 weeks
Functional Connectivity Changes in the Brain
Neuroimaging using PET/MRI to determine Functional Connectivity in Default Mode Network (DMN) and Central Executive Network (CEN) systems in the brain following rTMS treatment. we will do this by doing ICA analysis for each network focused from the stimulation site.
Time frame: 2-4 weeks
Quality of Life measure: Short Form of Veterans Rand 36 Item Health Survey (SF/VR-36)
Measure of Quality of Life change following rTMS treatment. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. We will look at these standardized eight scores as outcomes measures as well as a total composite score as an outcome measure.
Time frame: 2-4 weeks
Sustained Improvement in primary Outcome Measure (CANTAB Paired Associates Learning (PAL)) at 6 months post-treatment
At 6-month follow-up, the study primary outcome, CANTAB Paired Associate Learning task will be assessed again to identify changes that are sustained due to treatment at six-months. This test has twenty-one outcome measures, covering the errors made by the participant, the number of trials required to locate the pattern(s) correctly, memory scores and stages completed (Administration time 10 minutes). The main score provided is the sum of pairs reproduced over three trials (range: 0-30). We will use the average number of trials needed to succeed on PAL task as the main outcome measure.
Time frame: 6 months
This study is completed, as verified in Apr 2023. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Palo Alto Veterans Institute for Research