Accelerated repetitive transcranial magnetic stimulation (rTMS) versus sham for post-stroke apathy

Accelerated rTMS for Post-stroke Apathy: A Double-blind Randomized Controlled Trial

This project will try a faster course of rTMS to see if it reduces persistent apathy in people at least six months after an ischemic or hemorrhagic stroke.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 40 Years and up
• Sex: All
• Sponsor: Medical University of South Carolina (other)
• Locations: 1 site (Charleston, South Carolina)
• Trial ID: NCT07113067 on ClinicalTrials.gov

What this trial studies

This is a randomized, double‑blind, sham‑controlled Phase 1/2 study testing an accelerated rTMS protocol targeting the dorsal medial prefrontal cortex (dmPFC)/medial prefrontal cortex using MRI‑guided neuronavigation. Participants aged 40 or older with persistent apathy after a stroke (AES ≥39) and intact cortex at the target site will receive either active or sham stimulation delivered in an accelerated schedule. The study will monitor safety, tolerability, and changes in apathy and related functional measures using standardized scales and cognitive testing. Investigators will also examine feasibility of personalized coil placement based on each participant’s post-stroke brain anatomy.

Who should consider this trial

Good fit: Ideal candidates are people aged 40 or older who are at least six months post ischemic or hemorrhagic stroke, have clinically significant apathy (AES ≥39), can undergo MRI and TMS, and can participate in testing with a caregiver/co‑participant available.

Not a fit: Patients with primary extra‑axial hemorrhage without ischemic stroke, other neurological disorders like dementia, moderate‑to‑severe global aphasia, visual impairment preventing testing, or contraindications to MRI or TMS are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the treatment could reduce apathy and improve motivation and participation in daily activities and rehabilitation for people with post-stroke apathy.

How similar studies have performed: Prior rTMS work targeting medial frontal circuits has shown promise for amotivation and apathy in other populations, but accelerated rTMS for post‑stroke apathy is an early and relatively novel approach.

Eligibility criteria

Inclusion Criteria:

* 40 years old or greater
* Right- or left-hemisphere ischemic or hemorrhagic stroke with at least 6 months chronicity
* Symptomatic apathy as confirmed by (A) total score on the Apathy Evaluation Scale by the participant or the caregiver/co-participant (AES) of ≥39
* Ability to participate in psychometric testing and cognitive tasks
* Intact cortex at the TMS target site as confirmed by pre-treatment MRI
* Ability to have a co-participant/caregiver who meets the criteria as detailed below.

Exclusion Criteria:

* Primary extra-axial hemorrhage (subdural or subarachnoid) without ischemic stroke or intraparenchymal hemorrhage
* Concomitant neurological disorders affecting motor or cognitive function (e.g. dementia)
* Moderate or severe global aphasia
* Visual impairment precluding completion of cognitive tasks
* Presence of contraindications to MRI or TMS including electrically, magnetically or mechanically activated metal or nonmetal implants such as cardiac pacemaker, intracerebral vascular clips or any other electrically sensitive support system;
* Pregnancy (to be later confirmed by UPT in any premenopausal female participants)
* History of a seizure disorder
* Preexisting scalp lesion, wound, bone defect, or hemicraniectomy
* Claustrophobia precluding ability to undergo an MRI
* Active substance use disorder
* Psychotic disorders
* Bipolar 1 Disorder
* Acute suicidality as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)30 or suicide attempt in the previous year

For CO-PARTICIPANT/CAREGIVER:

Inclusion Criteria:

* Age 18 years or older
* Is a reliable informant who has at least weekly contact with the participant and can speak to the participant's cognitive and everyday functioning.

Exclusion Criteria:

\- Unable to engage with study procedures in which Co-Participant input is needed.

Where this trial is running

Charleston, South Carolina

• Medical University of South Carolina Brain Stimulation Lab — Charleston, South Carolina, United States (RECRUITING)

Study contacts

• Principal investigator: Parneet Grewal, PhD — Medical University of South Carolina
• Study coordinator: Parneet Grewal, MD

Conditions: Apathy, Stroke, Stroke Sequelae, Stroke/Brain Attack, Stroke/ Cerebrovascular Accident, Motivation, Abulia, Depression