Accelerated TMS for Apathy in PD

NCT07399496 | Recruiting DMC FDA Device

• 1 other identifier: Pro00147039
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This single-site, open-label pilot study will evaluate the feasibility, tolerability, and preliminary efficacy of accelerated intermittent theta-burst stimulation (iTBS) targeting the dorsomedial prefrontal cortex (dmPFC) for apathy in individuals with Parkinson's Disease (PD). Fifteen participants with PD and clinically significant apathy will undergo six treatment visits over two weeks, receiving eight iTBS sessions per day. Outcomes include adherence, tolerability, changes in apathy (Lille Apathy Rating Scale), functional engagement, and neural target engagement assessed via resting-state fMRI and EEG. Follow-up assessments will occur at two and four weeks post-treatment.

Conditions

Parkinson Disease

Keywords

Neuromodulation; iTBS; Transcranial Magnetic Stimulation; Apathy; Parkinson's Disease

Outcome Measures

Primary Outcomes (4)

• TMS adherence

  Proportion of planned accelerated iTBS sessions completed. Adherence is calculated as number of iTBS sessions completed out of 48 scheduled sessions (6 treatment days × 8 sessions/day).

  Day 1 through Day 14 (6 treatment days over approximately 2 weeks)

• Frequency and Severity of TMS-Induced Side effects (TMS tolerability and acceptability)

  Participant-reported tolerability/acceptability assessed with a standardized questionnaire capturing frequency and severity of common TMS side effects (e.g., headache, pain, scalp irritation, facial twitching, fatigue, fear/anxiety), collected during treatment days (pre/post sessions).

  Measured during each treatment day (6 days within a 2-week period)

• Apathy severity as measured by the Lille Apathy Rating Scale

  Change in apathy measured by the Lille Apathy Rating Scale (LARS) patient and caregiver/informant versions; analyzed as change from baseline to post-treatment and follow-up timepoints. Possible scores range from -36 to 36 with higher scores indicating greater apathy.

  Baseline (Day 0), immediately post-treatment (Day 14), 2 weeks post-treatment, and 4 weeks post-treatment

• Target engagement (dmPFC network modulation)

  Change in dmPFC target engagement measured by (1) resting-state fMRI functional connectivity of dmPFC to motivation/effort-related nodes and (2) EEG waveform/response metrics during motivation/effort tasks, comparing pre- vs post-intervention.

  Baseline MRI/EEG assessments (Days 0-1) and post-treatment MRI/EEG assessments (Days 14-15)

Secondary Outcomes (3)

• Goal attainment

  Baseline (Day 0), immediately post-treatment (Day 14), 2 weeks post-treatment, and 4 weeks post-treatment

• Change in apathy as measured by the Dimensional Apathy Scale

  Baseline (Day 0), immediately post-treatment (Day 14), 2 weeks post-treatment, and 4 weeks post-treatment"

• Change in apathy-related behavior as measured by the Frontal Systems Behavior Scale

  Baseline (Day 0), immediately post-treatment (Day 14), 2 weeks post-treatment, and 4 weeks post-treatment"

Study Arms (1)

TMS group

OTHER

participants with Parkinson's disease and clinically significant apathy receive accelerated iTBS rTMS targeting the left dorsomedial prefrontal cortex (dmPFC) using a MagVenture MagPro system with a cooled figure-of-eight coil and Brainsight neuronavigation (slightly off midline). Resting motor threshold (rMT) is determined on the first stimulation visit (PEST) and stimulation is delivered at 120% rMT. Treatment occurs on 6 days over \~2 weeks (days may be non-contiguous), with 8 sessions/day separated by 10-15 min. Each session delivers 600 pulses (50 Hz triplets; 2 s on/8 s off; \~190 s), totaling 4,800 pulses/day and 28,800 pulses overall. Coil position/angle and scalp-to-cortex distance are tracked; tolerability/acceptability (headache, pain, scalp irritation, facial twitching, fatigue, fear/anxiety) is assessed before/after sessions.

Device: Accelerated intermittent theta-burst stimulation (iTBS) rTMS to left dorsomedial prefrontal cortex (dmPFC)

Interventions

Accelerated intermittent theta-burst stimulation (iTBS) rTMS to left dorsomedial prefrontal cortex (dmPFC) DEVICE

Accelerated intermittent theta-burst stimulation (iTBS) rTMS to left dorsomedial prefrontal cortex (dmPFC) (MagVenture MagPro with cooled figure-of-eight coil; Brainsight neuronavigation; 120% rMT; 6 treatment days over \~2 weeks; 8 sessions/day; 600 pulses/session; 10-15 min inter-session interval).

TMS group

Eligibility Criteria

• Age: 45 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 45-85
• Diagnosis of Parkinson's Disease
• AES ≥37
• Stable PD medications
• Caregiver informant available

You may not qualify if:

• MRI/TMS contraindications
• Severe cognitive impairment (MoCA \<21)
• Psychiatric disorders (bipolar, schizophrenia, active substance use disorder)
• Seizure history
• Acute suicidality as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) or suicide attempt in the previous year
• Pregnancy

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (1)

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

MeSH Terms

Conditions

Parkinson Disease; Lethargy

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Daniel Lench

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 7, 2026
• First Posted: February 10, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

US (1)