NCT05878457

Accelerated rTMS for Post-Stroke Apathy

Accelerated rTMS for Post-Stroke Apathy: Targeting Amotivation Toward Improving Whole Health and Rehabilitation Engagement

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: Medical University of South Carolina · Academic / Other
• Sex: All
• Age: 40 Years
• Healthy volunteers: Not accepted

Summary

This pilot study will investigate the safety, feasibility, tolerability, and preliminary efficacy of accelerated high-dose repetitive transcranial magnetic stimulation (rTMS) targeting the medial prefrontal cortex (mPFC) to address apathy symptoms in individuals with chronic stroke.

Detailed description

Repetitive transcranial magnetic stimulation (rTMS) is a well-established FDA-approved treatment for several psychiatric indications including treatment-resistant depression, obsessive-compulsive disorder, and smoking cessation. Traditional rTMS targets the dorsolateral prefrontal cortex (dlPFC) with repetitive treatments delivered for six weeks. Recent innovations have led to the development of accelerated, high-dose rTMS protocols, with recent FDA-approval, that are capable of delivering a full treatment course within a single week. Accumulating evidence suggests that similar neuromodulation protocols may be helpful in targeting neuropsychiatric symptoms across a range of neurologic and neurodegenerative conditions including dementia, movement disorders, and stroke. Apathy is a distinct neuropsychiatric symptom characterized by loss of motivation, withdrawal, and decreased goal-directed activity seen across a wide range of neuropsychiatric conditions. Apathy contributes significantly to lower quality of life, caregiver burnout, and poorer rehabilitation outcomes. Meanwhile, there are currently no FDA-approved treatments targeting apathy specifically. The mPFC has been well-established as a safe and feasible target for traditional rTMS, and may be a desirable stimulation site in targeting apathy due to its superficial location and integral association with other brain structures implicated in apathy pathophysiology such as the anterior cingulate cortex (ACC) and ventral striatum (VL). This phase I open-label pilot study will investigate high-dose, accelerated rTMS at the medial prefrontal cortex (mPFC) to target apathy in individuals with chronic stroke. The primary aims of the study will be to: (1) establish the safety, feasibility, tolerability, and acceptability of an accelerated repetitive transcranial magnetic stimulation (rTMS) protocol for apathy in chronic stroke; (2) establish the feasibility of individualized resting-state functional magnetic resonance imaging (fMRI) connectivity for targeting rTMS in post-stroke apathy; (3) establish preliminary efficacy of an accelerated rTMS protocol for post-stroke apathy. Given the limited power of this small pilot study, this aim will be considered exploratory with the intention to guide future research. Sixteen chronic stroke patients with symptomatic apathy will complete (1) structural as well as resting state functional MRI at baseline for targeting parcellations. (2) A battery of validated clinical assessments of apathy-related symptoms (3) a battery of neuropsychological, cognitive, and symptom measures to assess safety, tolerability, and feasibility. Treatment will consist of open-label, high-dose rTMS to left mPFC delivered following a standard protocol consisting of 600 pulses, twelve times per day, for three treatment days (contiguous or non-contiguous) within a seven-day period. Safety assessments will be monitored throughout treatment. A battery of clinical assessments will be repeated at the end of treatment and weekly for one month post-treatment.

Conditions

• Apathy
• Stroke Sequelae
• Stroke (CVA) or TIA
• Stroke/Brain Attack
• Motivation
• Abulia

Interventions

Type	Name	Description
DEVICE	MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System	Treatment will consist 12 approximately-three-minute sessions on each of three treatment days within a seven-day period. To promote participant adherence and retention, treatment days will not need to be contiguous. A single session consists of 600 pulses delivered to the dmPFC at an intensity of 120% resting motor threshold (rMT). 50 hz triphasic bursts will be delivered for two seconds, followed by an 8 second inter-train interval. Trains will be repeated every 10 seconds, 10 times total, for a total of 190 seconds per session. An intersession interval of at least 15 minutes will be employed between each of the 12 sessions. Each treatment day will thus last approximately 3-4 hours in duration.

Timeline

• Start date: 2023-12-01
• Primary completion: 2025-04-30
• Completion: 2025-04-30
• First posted: 2023-05-26
• Last updated: 2025-06-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated device study