Investigating the Neural Mechanisms of Repetitive Brain Stimulation With Invasive and Noninvasive Electrophysiology in Humans

Sponsor

Stanford University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05996900

Collaborator

University of Iowa (Other), Massachusetts General Hospital (Other)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder Epilepsy	Device: Intracranial electrodes Device: TMS	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

49 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

Investigating the Neural Mechanisms of Repetitive Brain Stimulation With Invasive and Noninvasive Electrophysiology in Humans

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2027

Anticipated Study Completion Date :

Jul 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: TBS via direct electrical stimulation	Device: Intracranial electrodes Intracranial electrodes will be used for the delivery of invasive brain stimulation.
Active Comparator: TBS via transcranial magnetic stimulation	Device: TMS TMS will be used for the delivery of noninvasive brain stimulation both before and after implantation electrode surgery.
Sham Comparator: Sham TBS via direct electrical stimulation	Device: Intracranial electrodes Intracranial electrodes will be used for the delivery of invasive brain stimulation.
Sham Comparator: Sham TBS via transcranial magnetic stimulation	Device: TMS TMS will be used for the delivery of noninvasive brain stimulation both before and after implantation electrode surgery.

Outcome Measures

Primary Outcome Measures

TMS-iEEG change after one TBS session [45 minutes]
Change in evoked response measured after a single TBS session for active and sham, by resting state iEEG (intracranial EEG) and/or sEEG (stereo EEG).

Secondary Outcome Measures

ES-iEEG change after one TBS session [45 minutes]
Change in evoked response measured after a single TBS session for active and sham, by resting state iEEG and/or sEEG.
ES-iEEG change between two sequential TBS sessions [45 minutes]
Change in single-pulse evoked response, or cortico-cortical evoked potentials (CCEPs), measured between two sequential TBS sessions, by resting state iEEG and/or sEEG.
TMS-iEEG change between two sequential TBS sessions [45 minutes]
Change in single-pulse evoked response, or cortico-cortical evoked potentials (CCEPs), measured between two sequential TBS sessions, by resting state iEEG and/or sEEG.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Stanford University
University of Iowa
Massachusetts General Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Corey Keller, Principal Investigator, Assistant Professor, Stanford University

ClinicalTrials.gov Identifier:

NCT05996900

Other Study ID Numbers:

132074

First Posted:

Aug 18, 2023

Last Update Posted:

Aug 18, 2023

Last Verified:

Aug 1, 2023

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Yes

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Depressive Disorder

Depressive Disorder, Major

Study Results

No Results Posted as of Aug 18, 2023