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

Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05996900
• Other study ID #: 11354-1
• Status: Active, not recruiting
• Phase: N/A
• Start date: September 1, 2023
• Est. completion date: July 1, 2028

Study information

• Verified date: December 2023
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 49
• Est. completion date: July 1, 2028
• Est. primary completion date: January 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Epilepsy
• Major Depressive Disorder

Intervention

Device:
• Intracranial electrodes
Intracranial electrodes will be used for the delivery of invasive brain stimulation.
• TMS
TMS will be used for the delivery of noninvasive brain stimulation both before and after implantation electrode surgery.

Locations

Country	Name	City	State
United States	Stanford University	Stanford	California

Sponsors (3)

Lead Sponsor	Collaborator
Stanford University	Massachusetts General Hospital, University of Iowa

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TMS-iEEG change after one TBS session	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).	45 minutes
Secondary	ES-iEEG change after one TBS session	Change in evoked response measured after a single TBS session for active and sham, by resting state iEEG and/or sEEG.	45 minutes
Secondary	ES-iEEG change between two sequential TBS sessions	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.	45 minutes
Secondary	TMS-iEEG change between two sequential TBS sessions	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.	45 minutes