Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT03727737 |
Other study ID # |
ADA0007AGG |
Secondary ID |
|
Status |
Completed |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
October 23, 2018 |
Est. completion date |
September 14, 2022 |
Study information
Verified date |
April 2023 |
Source |
Palo Alto Veterans Institute for Research |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial 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.
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).