Clinical trial NCT05996900: Investigating the Neural Mechanisms of Repetitive Brain Stimulation With Invasive and Noninvasive Electrophysiology in Humans
Official title: Investigating the Neural Mechanisms of Repetitive Brain Stimulation With Invasive and Noninvasive Electrophysiology in Humans
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Major Depressive Disorder
Epilepsy
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: University of Iowa
name: Massachusetts General Hospital
First posted: 2023-08-18
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Transcranial magnetic stimulation (TMS) is an effective treatment for depression, but clinical outcome is suboptimal, partially because investigators are missing biologically-grounded brain markers which show that TMS is modifying activity at the intended target in the brain. The goal of this proposal is to characterize the key markers of the brain's response to repeated doses of TMS with high resolution using invasive brain recordings in humans, and relate these brain markers to noninvasive recordings. These markers will improve the understanding of TMS and can be used to optimize and enhance clinical efficacy for depression and other psychiatric disorders.

Detailed description: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder, but remission rates are 20-40%, and ideal stimulation parameters are unknown. rTMS is thought to work by changing the synaptic strength of neurons. The ability of the brain to make these changes is referred to as plasticity. rTMS-induced changes are thought to build with successive treatment sessions, a process referred to as metaplasticity. While both plasticity and metaplasticity are well-established in single cell physiology, relevance to rTMS in humans remains unknown. To improve clinical efficacy, the investigators need to understand 1) the neural response to a single rTMS session (plasticity), 2) the neural response to repeated daily rTMS sessions (metaplasticity), and 3) whether computational models of plasticity based on single-cell physiology apply to human patients receiving rTMS for depression.

Goals of the study are to 1) establish a detailed mechanistic understanding of the brain changes during current rTMS treatment; 2) identify clinically meaningful electrophysiological biomarkers for rTMS treatment; 3) establish a computational model to help predict both brain and clinical changes.

Eligibility criteria: Inclusion Criteria:

* Men and women, ages 18 to 65
* Medication-refractory epilepsy requiring phase II monitoring
* Must have intellectual capacity to ensure adequate comprehension of the study and potential risks involved in order to provide informed consent
* No current or history of major neurological disorders other than epilepsy

Exclusion Criteria:

* Those with a contraindication for MRIs (e.g. implanted metal)
* Any unstable medical condition
* Neurological or uncontrolled medical disease
* Active substance abuse
* Currently pregnant or breastfeeding

Primary outcomes:
measure: TMS-iEEG change after one TBS session
timeFrame: 45 minutes
Secondary outcomes:
measure: ES-iEEG change after one TBS session
timeFrame: 45 minutes
measure: ES-iEEG change between two sequential TBS sessions
timeFrame: 45 minutes
measure: TMS-iEEG change between two sequential TBS sessions
timeFrame: 45 minutes
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
References: