Accelerated rTMS for Post-Stroke Apathy

NCT05878457 | Completed Phase 1 DMC FDA Device

• 1 other identifier: Pro00126436
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (6)

• Change in apathy symptoms, as measured by the Lille Apathy Rating Scale (LARS) compared to baseline

  The Lille Apathy Rating Scale (LARS) is a clinically validated 33-item structured interview assessing clinical symptoms of apathy. The structured interview is broken into 9 sub-scales including everyday productivity, interests, taking the initiative, novelty seeking, motivation, emotional responsiveness, concern, and social life. Total scores can range from -36 to +36 and are further stratified by factorial sub-scores including intellectual curiosity, emotion, action initiation, and self-awareness.

  Pre-treatment, immediately post-treatment, and weekly for four weeks post-treatment

• Incidence of Treatment-Emergent Adverse Events and Side Effects as assessed by change in the Review of Systems Criteria compared to baseline

  A review of systems questionnaire will be administered to rate the subjective symptom (headache, scalp pain, arm/hand pain, other pain(s), numbness/tingling, other sensation(s), weakness, loss of dexterity, vision/hearing change(s), ear ringing, nausea/vomiting, appetite loss, rash, skin change(s) or any other symptom(s)) on a scale of 0 to 5 (none, minimal, mild, moderate, marked, severe).

  After each session of rTMS during each of three treatment days within one week

• Change in global cognition, as measured by the Montreal Cognitive Assessment (MoCA) compared to baseline

  The Montreal Cognitive Assessment (MoCA) is a clinical assessment of cognitive function. The MoCA assesses multiple cognitive domains including memory, visuospatial skills, executive function, attention, concentration, calculation, language, abstraction, and orientation. The MoCA can be administered in approximately 10 minutes and total scores range from 0 to 30 with lower scores correlating with greater degree of cognitive impairment.

  Pre-treatment, immediately post-treatment, and at one month post-treatment follow-up

• Change From Baseline Cognition, as Measured by the Fluid Cognition Composite Score From the NIH Toolbox Cognition Battery compared to baseline

  Fluid cognition was measured using the iPad-administered NIH Toolbox Cognition Battery (NIHTB-CB). Fluid Cognition Composite scores were calculated by averaging the demographically adjusted (age, education, sex, race/ethnicity; Casaletto et al., 2015) T-scores for 4 NIHTB-CB tests: the flanker inhibitory control, list sorting working memory, pattern comparison processing speed, and dimensional change card sort tests. T-Scores have a mean of 50 and a standard deviation of 10. Lower scores indicate worse performance.

  Pre-treatment, immediately post-treatment

• Participant retention rate

  Percentage of participants who completed the study relative to all participants who initiated treatment (target n=16). Percentage of participants who completed the study relative to all participants who initiated treatment (target n=16). Percentage of participants who completed the study relative to all participants who initiated treatment (target n=16).

  calculated at the end of the study follow-up assessment period (one month post-treatment)

• Patient perception of treatment acceptability as assessed by study-specific questionnaire

  A 15-item study-specific questionnaire of rTMS treatment acceptability, with each item rated on a scale from 1 to 5 (1 = not at all, 3 = somewhat, 5 = very much so). Higher scores indicate better acceptability for the first 10 items, lower scores indicate better acceptability for the last 5 items.

  After each session of rTMS during each of three treatment days within one week, and at one month post-treatment follow-up

Secondary Outcomes (2)

• Change in apathy symptoms, as measured by the Apathy Evaluation Scale (AES) compared to baseline

  Pre-treatment, immediately post-treatment, and at one month post-treatment follow-up

• Patient-Reported Outcomes Measurement Information System (PROMIS) Depression Short Form

  Pre-treatment, immediately post-treatment, and weekly for four weeks post-treatment

Study Arms (1)

Repetitive transcranial magnetic stimulation

EXPERIMENTAL

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.

Device: MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System

Interventions

MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System 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.

Also known as: Brainsight Neuronavigation System

Repetitive transcranial magnetic stimulation

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (AES) of ≥39 as rated by the participant or caregiver informant
• Intact cortex under the coil at the stimulation target site confirmed by neuroimaging
• Ability to participate in psychometric testing and cognitive tasks

You may not qualify if:

• 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 pacemakers, 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 the 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) or suicide attempt in the previous year

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (1)

Medical University of South Carolina Brain Stimulation Lab

Charleston, South Carolina, 29403, United States

Location

Related Publications (11)

• 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.

  PMID: 28689673 BACKGROUND

• 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.

  PMID: 16207933 BACKGROUND

• 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.

  PMID: 20734360 RESULT

• 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.

  PMID: 28578330 RESULT

• 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.

  PMID: 19008681 RESULT

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

  PMID: 20540829 RESULT

• 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.

  PMID: 15817019 RESULT

• 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.

  PMID: 16614016 RESULT

• 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.

  PMID: 26030001 RESULT

• 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.

  PMID: 26931289 RESULT

• 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.

  PMID: 1754629 RESULT

MeSH Terms

Conditions

Lethargy; Stroke

Interventions

Transcranial Magnetic Stimulation; Drug Delivery Systems

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics; Drug Therapy

Study Officials

• Parneet Grewal, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DEVICE FEASIBILITY
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor-Faculty

Model Details: single group, open-label pilot investigation

Study Record Dates

• First Submitted: April 20, 2023
• First Posted: May 26, 2023
• Study Start: December 1, 2023
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: June 12, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)