Transcranial Magnetic Stimulation for MCI — PUSH2  

Depression Clinical Trial

Official title: Transcranial Magnetic Stimulation for MCI: A Phase II Dose-Response Study

Status Recruiting

Clinical Trial Summary

The goal of this phase II study is to establish the dose-response curves of a safe and clinically feasible non-invasive brain stimulation technique (accelerated Transcranial Magnetic Stimulation (TMS)) to improve both depression and cognitive function in Mild Cognitive Impairment (MCI) patients with comorbid depression. It is known that TMS can effectively treat depression. Identifying the right dose of accelerated TMS in MCI patients is necessary prior to designing subsequent trials to determine efficacy. These results will inform future clinical trials of accelerated TMS for MCI, with the long-term goal of developing an efficacious treatment to prevent dementia.

Clinical Trial Description

Mild Cognitive Impairment (MCI) is a heterogenous syndrome of cognitive and neuropsychiatric symptoms, with as much as 40% of patients being diagnosed with comorbid depression. The goal of this phase II trial is to establish the functional form of the dose-response curves for accelerated intermittent theta burst stimulation (iTBS) to ameliorate depression and cognitive function in MCI. Identifying the right dose is necessary prior to designing subsequent trials to ascertain the efficacy of accelerated iTBS for MCI. In our two phase I trials, we chose treatment parameters based on robust prior literature on accelerated, high-dose rTMS delivery (i.e. accelerated iTBS, 600 pulses at 50 Hz per session), intensity (at 120% resting motor threshold [rMT]), stimulation site left dorsolateral prefrontal cortex (l-dlPFC), and site targeting (Beam F3). The course of treatment was guided by our clinical experience with mild cognitive impairment and vascular cognitive impairment patients as to what we hypothesized they would comfortably tolerate, which was confirmed by the acceptability ratings. In this phase II trial, we focus on manipulating one dosing parameter

• total number of active pulses - to rigorously model the dose-response curves such that future phase II/III trials can be more efficient, decrease treatment burden, and accelerate response time.

Aim 1: Establish the dose-response curves for reduced depression following accelerated iTBS in MCI.

Aim 2: Establish the dose-response curves for improved cognition following accelerated iTBS in MCI.

Exploratory Aim 1: Examine alterations in functional connectivity following accelerated iTBS-rTMS in MCI.

Exploratory Aim 2: Examine blood-based biomarkers of neurodegeneration as effect modifiers. ;

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Depression
• Mild Cognitive Impairment

• NCT number: NCT05992831
• Study type: Interventional
• Source: Medical University of South Carolina
• Contact: Andreana Benitez, PhD
• Phone: 843-876-2479
• Email: benitez@musc.edu
• Status: Recruiting
• Phase: N/A
• Start date: July 15, 2024
• Completion date: April 30, 2028