Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05224063 |
| Other study ID # |
60980-2 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2023 |
| Est. completion date |
June 30, 2025 |
Study information
| Verified date |
December 2023 |
| Source |
Stanford University |
| Contact |
Corey Keller, MD, PhD |
| Phone |
(650) 498-9111 |
| Email |
kellerlab[@]stanford.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Depression is a highly prevalent condition characterized by persistent low mood, energy, and
activity that can affect one's thoughts, mood, behavior, and sense of well-being. Repetitive
transcranial magnetic stimulation (rTMS), a non-invasive neuromodulatory technique, is an
effective treatment for depression when targeting the dorsolateral prefrontal cortex (dlPFC)
of the central executive network (CEN). However, remission rates are suboptimal and
individual methods to target the dlPFC are lacking. In this study, we will enroll 50 patients
with major depression and in a single rTMS 'dose,' prospective, randomized, double-blind,
cross-over design will assess whether rTMS targeted to an individual's central executive
network (CEN) assessed by single pulse TMS can enhance network modulation. If successful,
this work will lead to a clinical rTMS trial comparing this personalized targeting approach
against standard rTMS.
Description:
There is a critical need for more effective treatments for depression, which currently affect
20% of Americans during our lifetimes. Brain stimulation treatments, including repetitive
transcranial magnetic stimulation (rTMS), represent the front line of innovative approaches
by directly targeting and correcting specific dysfunctional brain networks. A core
dysfunctional network in major depressive disorder is the fronto-parietal central executive
network (CEN), a network critical for decision making and cognitive control. The CEN includes
the dorsolateral prefrontal cortex (dlPFC), the target of FDA-cleared rTMS treatment for
depression. rTMS to the dlPFC is thought to improve depression by modulating local dlPFC
excitability and enhancing downstream CEN connectivity. However, our ability to probe the CEN
and study this potential mechanism on an individual basis is critically lacking, likely
contributing to suboptimal rTMS remission rates (20-40%). We hypothesize that the CEN
connectivity is weakened in depression and can be maximally modulated by individualizing
localization.
To test this hypothesis, in a single rTMS 'dose,' prospective, randomized, double-blind,
cross-over design with 50 depressed patients, we will prospectively compare the strength,
duration, and specificity of CEN modulation after a single session of dlPFC rTMS. These
participants will be 18-65 years old and require a current major depressive disorder
diagnosis assessed by Structured Clinical Interview for DSM5 (SCID-I62), with a PHQ9>10.
Exclusion criteria includes contraindications for MRIs (e.g. implanted metal), history of
head trauma with loss of consciousness, history of seizures, neurological or uncontrolled
medical disease, active substance abuse, a history of suicide attempt in the past year,
psychotic or bipolar disorders, a prior history of ECT or rTMS failure, and medications that
substantially reduce seizure threshold (e.g., bupropion, clozapine).
Following the diagnostic session, participants will undergo a 30-minute MRI session to record
structural brain data. For the following sessions, dlPFC will be targeted for each session
using different methods and 10Hz dlPFC rTMS will be applied guided by (a) individualized CEN
targeting, (b) structural MRI, (c) standard scalp targeting. For each condition, a single
session of rTMS at standard parameters (10Hz, 5s on, 10s off, 3,000 total pulses, 15 min
duration) will be performed and changes in CEN connectivity will be quantified using pre/post
dlPFC-stimulated parietal TMS-evoked potentials (TEPs). The dlPFC will be targeted for rTMS
using three methods: (a) MRI-guided with individual CEN optimization using TEPs, (b)
MRI-guided alone, and (c) standard scalp targeting (Beam F3 method99). Additionally, a fourth
session of sham rTMS will be applied to control for off-target effects. We hypothesize that
while each active rTMS method (condition a-c) will suppress the p30 of the TEP in the CEN,
optimized CEN localization using individual TEPs (condition a) will induce the strongest and
most specific change in the CEN for the longest duration. Our primary outcome will be
parietal p30 CEN modulation directly following rTMS. Secondary outcomes will assess parietal
p30 changes in the parietal node of the CEN during rTMS (quantifying the p30 after the last
pulse in each stimulation train) as well as 15 and 30 min following rTMS. We will also assess
pre/post rTMS behavioral changes in attention with a standard continuous performance task and
working memory using an N-back task, both of which have been implicated in the CEN and
depression100,101. rTMS sessions will be triple-blinded to operator, participant, and
statistician. rTMS sessions will be separated by at least two days to remove potential
lasting effects >24 hours, and rTMS session order will be randomized and counterbalanced to
reduce any potential bias.
Findings from this study will provide the basis for a clinical trial comparing rTMS treatment
outcome using this personalized targeting approach against standard rTMS.
