Accelerated Transcranial Magnetic Stimulation (TMS) for Apathy in Parkinson's Disease
Overview
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- TMS adherence
Overview
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.
Detailed Description
This study is designed to explore a new treatment option for people with Parkinson's disease who experience apathy, which means loss of motivation or interest in daily activities. Apathy is common in Parkinson's disease and can lower quality of life, but current treatments are limited. Investigators are testing whether a non-invasive brain stimulation technique called repetitive transcranial magnetic stimulation (rTMS) is tolerable, acceptable and can be used to improve apathy in patients with Parkinson's disease. TMS delivers brief magnetic pulses to specific areas of the brain that are linked to motivation and decision-making. In this study, Investigators will use an "accelerated" version of TMS, which gives several short sessions in a single day, reducing the number of visits required. The purpose of this research is to see whether this treatment approach is feasible, tolerable and and potentially effective at treating apathy in people with Parkinson's disease. If successful, this research study will hopefully lead to a larger study in the future where the efficacy of the treatments can be studied.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 45 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 45-85
- •Diagnosis of Parkinson's Disease
- •Stable PD medications
- •Caregiver informant available
Exclusion Criteria
- •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
Arms & Interventions
TMS group
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.
Intervention: Accelerated intermittent theta-burst stimulation (iTBS) rTMS to left dorsomedial prefrontal cortex (dmPFC) (Device)
Outcomes
Primary Outcomes
TMS adherence
Time Frame: Day 1 through Day 14 (6 treatment days over approximately 2 weeks)
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).
Target engagement (dmPFC network modulation)
Time Frame: Baseline MRI/EEG assessments (Days 0-1) and post-treatment MRI/EEG assessments (Days 14-15)
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.
Frequency and Severity of TMS-Induced Side effects (TMS tolerability and acceptability)
Time Frame: Measured during each treatment day (6 days within a 2-week period)
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).
Apathy severity as measured by the Lille Apathy Rating Scale
Time Frame: Baseline (Day 0), immediately post-treatment (Day 14), 2 weeks post-treatment, and 4 weeks post-treatment
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.
Secondary Outcomes
- 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")
Investigators
Daniel Lench
Assistant Professor
Medical University of South Carolina