NCT05992831

Transcranial Magnetic Stimulation for MCI

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

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Medical University of South Carolina · Academic / Other
• Sex: All
• Age: 60 Years – 85 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

• Mild Cognitive Impairment
• Depression

Interventions

Type	Name	Description
DEVICE	Accelerated iTBS	The investigators will treat participants with accelerated intermittent theta burst stimulation. iTBS will be delivered via a MagVenture MagPro TMS System with a Cool-B65 coil, targeting to direct the stimulation to the left dorsolateral prefrontal cortex (l-dlPFC). The investigators will use a standard resting motor threshold (rMT) determination to determine the TMS dose. Treatment will be delivered at 120% of the motor threshold. Total treatment time will be controlled; all participants will perceive receiving active treatment for 10 3-min sessions with 10-15 min inter-session intervals, resulting in a 3-hour treatment day. At pre-treatment, a focal electrical sham will be individually titrated to participant tolerability. Participants then receive an individualized level of sham stimulation throughout treatment, to bolster the blind. Participants will be told that they will be receiving different doses throughout the treatment day, again to maintain the integrity of the blind.
DEVICE	Sham Comparator	To achieve adequate blinding, participants will go through the same number of sessions per day irrespective of the active and/or sham dose-step combination to which they are assigned. Sham sessions will be assigned in random order over the 10 sessions. The sequence of active and/or sham sessions for each treatment day is assigned a random code that is entered into the TMS system by the coordinator to maintain the integrity of the blind.

Timeline

• Start date: 2024-06-18
• Primary completion: 2028-04-30
• Completion: 2028-04-30
• First posted: 2023-08-15
• Last updated: 2026-04-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated device study