Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT03702127 |
| Other study ID # |
201707763 |
| Secondary ID |
|
| Status |
Enrolling by invitation |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 16, 2019 |
| Est. completion date |
July 30, 2026 |
Study information
| Verified date |
July 2023 |
| Source |
University of Iowa |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This is a study looking at the effects of transcranial magnetic stimulation (TMS), a form of
non-invasive brain stimulation (NIBS), on the human brain as recorded by intracranial
electroencephalography in neurosurgical patients. NIBS will be applied in a targeted manner
and brain responses will be recorded.
Description:
In the last few years, non-invasive brain stimulation techniques such as transcranial
magnetic stimulation (TMS), transcranial current stimulation, and peripheral multi-modal
stimulation have shown widespread clinical applications. Transcranial magnetic stimulation
(TMS) is a noninvasive method of focally stimulating the brain that uses electromagnetic
induction and does not require surgery. There is optimism that TMS and other forms of NIBS
will revolutionize how we treat neurological and psychiatric disorders, evidenced by over
1000 clinical trials registered using TMS. Much of this optimism stems from the successful
use of TMS as a treatment for depression. Despite the large number of clinical trials using
NIBS the number of therapeutic indications has been stagnant, limited to major depression and
more recently obsessive-compulsive disorder. There are fundamental questions about the
underlying mechanisms of action for NIBS that will be critical to understand in order to
advance this treatment modality. Here, we propose a unique collaborative project between
neurology and neurosurgery that will allow an unprecedented window into understanding how
NIBS impacts the human brain. Specifically, we will perform various forms of targeted TMS in
neurosurgical patients with intracranial electroencephalography (iEEG) monitoring to record
real time effects of NIBS on local and remote brain areas with an unparalleled combination of
spatial and temporal resolution relative to other human studies. TMS may present the most
risk for patients with intracranial electrodes and we have already demonstrated the safety of
this approach using a gel-based phantom brain and have results from seven patients
demonstrating safety and preliminary results. For the current proposal we aim to: 1)
characterize the response of NIBS on the human brain as recorded from iEEG between active and
sham conditions, and 2) relate remote electrophysiological responses from NIBS to measures of
brain connectivity between the stimulation & recording sites assessed with resting state
functional connectivity MRI (rs-fcMRI). This will allow us to evaluate the relationship
between NIBS-evoked iEEG responses and the strength of functional connectivity to the
stimulation site in a regression model. For the TMS portion of the study we hypothesize that
1) TMS will have focal effects detected from surface electrodes underlying the stimulation
site as well as network-level engagement detected at remote sites, 2) Repetitive TMS will
induce frequency-specific effects that differ between 0.5 and 10 Hz stimulation protocols,
and 3) the magnitude of repetitive TMS-evoked iEEG responses across electrodes will relate to
the strength of rs-fcMRI between the stimulation and recording sites. By investigating the
electrophysiological responses of TMS with high spatiotemporal precision in humans, this
study will provide new mechanistic insights into the effects of TMS on target engagement and
relate these findings to imaging methods already in widespread use. Moreover, the TMS will be
applied in a clinically meaningful way by targeting the left dorsolateral prefrontal cortex
in a protocol used to treat depression. Generating results for these aims will be key to
advancing our understanding of how TMS and other forms of NIBS engage brain networks, which
can be leveraged to rationally develop personalized, imaging-guided therapeutic NIBS for
depression and other disorders.
