Accelerated rTMS for Post-Stroke Apathy

NCT ID: NCT05878457

Last Updated: 2025-06-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

14 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-12-01

Study Completion Date

2025-04-30

Brief Summary

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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

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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

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

single group, open-label pilot investigation
Primary Study Purpose

DEVICE_FEASIBILITY

Blinding Strategy

NONE

Study Groups

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Repetitive transcranial magnetic stimulation

All participants will receive accelerated, high-dose repetitive transcranial magnetic stimulation (rTMS) at the medial prefrontal cortex (mPFC) delivered in runs of 600 pulses, twelve times per day, for three treatment days (contiguous or non-contiguous) within a seven-day period.

Group Type EXPERIMENTAL

MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System

Intervention Type DEVICE

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.

Interventions

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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.

Intervention Type DEVICE

Other Intervention Names

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Brainsight Neuronavigation System

Eligibility Criteria

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Inclusion Criteria

1. 40 years old or greater
2. Right- or left-hemisphere ischemic or hemorrhagic stroke with at least 6 months chronicity
3. Symptomatic apathy as confirmed by (A) total score on the Apathy Evaluation Scale (AES) of ≥39 as rated by the participant or caregiver informant
4. Intact cortex under the coil at the stimulation target site confirmed by neuroimaging
5. Ability to participate in psychometric testing and cognitive tasks

Exclusion Criteria

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

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medical University of South Carolina

OTHER

Sponsor Role lead

Responsible Party

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Parneet Grewal

Assistant Professor-Faculty

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Parneet Grewal, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

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Medical University of South Carolina Brain Stimulation Lab

Charleston, South Carolina, United States

Site Status

Countries

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United States

References

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Le Heron C, Apps MAJ, Husain M. The anatomy of apathy: A neurocognitive framework for amotivated behaviour. Neuropsychologia. 2018 Sep;118(Pt B):54-67. doi: 10.1016/j.neuropsychologia.2017.07.003. Epub 2017 Jul 8.

Reference Type BACKGROUND
PMID: 28689673 (View on PubMed)

Levy R, Dubois B. Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits. Cereb Cortex. 2006 Jul;16(7):916-28. doi: 10.1093/cercor/bhj043. Epub 2005 Oct 5.

Reference Type BACKGROUND
PMID: 16207933 (View on PubMed)

Holtzheimer PE 3rd, McDonald WM, Mufti M, Kelley ME, Quinn S, Corso G, Epstein CM. Accelerated repetitive transcranial magnetic stimulation for treatment-resistant depression. Depress Anxiety. 2010 Oct;27(10):960-3. doi: 10.1002/da.20731.

Reference Type RESULT
PMID: 20734360 (View on PubMed)

Sasaki N, Hara T, Yamada N, Niimi M, Kakuda W, Abo M. The Efficacy of High-Frequency Repetitive Transcranial Magnetic Stimulation for Improving Apathy in Chronic Stroke Patients. Eur Neurol. 2017;78(1-2):28-32. doi: 10.1159/000477440. Epub 2017 Jun 3.

Reference Type RESULT
PMID: 28578330 (View on PubMed)

Santa N, Sugimori H, Kusuda K, Yamashita Y, Ibayashi S, Iida M. Apathy and functional recovery following first-ever stroke. Int J Rehabil Res. 2008 Dec;31(4):321-6. doi: 10.1097/MRR.0b013e3282fc0f0e.

Reference Type RESULT
PMID: 19008681 (View on PubMed)

Jorge RE, Starkstein SE, Robinson RG. Apathy following stroke. Can J Psychiatry. 2010 Jun;55(6):350-4. doi: 10.1177/070674371005500603.

Reference Type RESULT
PMID: 20540829 (View on PubMed)

Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.

Reference Type RESULT
PMID: 15817019 (View on PubMed)

Sockeel P, Dujardin K, Devos D, Deneve C, Destee A, Defebvre L. The Lille apathy rating scale (LARS), a new instrument for detecting and quantifying apathy: validation in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2006 May;77(5):579-84. doi: 10.1136/jnnp.2005.075929.

Reference Type RESULT
PMID: 16614016 (View on PubMed)

Casaletto KB, Umlauf A, Beaumont J, Gershon R, Slotkin J, Akshoomoff N, Heaton RK. Demographically Corrected Normative Standards for the English Version of the NIH Toolbox Cognition Battery. J Int Neuropsychol Soc. 2015 May;21(5):378-91. doi: 10.1017/S1355617715000351. Epub 2015 Jun 1.

Reference Type RESULT
PMID: 26030001 (View on PubMed)

Schalet BD, Pilkonis PA, Yu L, Dodds N, Johnston KL, Yount S, Riley W, Cella D. Clinical validity of PROMIS Depression, Anxiety, and Anger across diverse clinical samples. J Clin Epidemiol. 2016 May;73:119-27. doi: 10.1016/j.jclinepi.2015.08.036. Epub 2016 Feb 27.

Reference Type RESULT
PMID: 26931289 (View on PubMed)

Marin RS, Biedrzycki RC, Firinciogullari S. Reliability and validity of the Apathy Evaluation Scale. Psychiatry Res. 1991 Aug;38(2):143-62. doi: 10.1016/0165-1781(91)90040-v.

Reference Type RESULT
PMID: 1754629 (View on PubMed)

Provided Documents

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Document Type: Informed Consent Form

View Document

Other Identifiers

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Pro00126436

Identifier Type: -

Identifier Source: org_study_id

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