Parkinson Disease
Conditions
Keywords
Neuromodulation, iTBS, Transcranial Magnetic Stimulation, Apathy, Parkinson's Disease
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.
Interventions
DEVICEAccelerated intermittent theta-burst stimulation (iTBS) rTMS to left dorsomedial prefrontal cortex (dmPFC)
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).
Sponsors
Medical University of South Carolina
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Age 45-85 * Diagnosis of Parkinson's Disease * AES ≥37 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TMS adherence | 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). |
| Frequency and Severity of TMS-Induced Side effects (TMS tolerability and acceptability) | 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 | 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. |
| Target engagement (dmPFC network modulation) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Goal attainment | Baseline (Day 0), immediately post-treatment (Day 14), 2 weeks post-treatment, and 4 weeks post-treatment | Change in goal-directed behavior measured by Bangor Goal-Setting Interview outcomes, including proportion/percent attainment of individualized goals across assessment timepoints. |
| 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 symptoms measured using the Dimensional Apathy Scale (DAS), including patient/informant reports where applicable. Scores range from 0-24 on each of the three subscales (executive, emotional, and behavior/ cognitive initiation) with higher scores indicating greater apathy. |
| 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" | Change in apathy-related symptoms measured using the Frontal Systems Behavior Scale (FRSBE), including patient/informant reports where applicable. Apathy components include 14 questions scored 0-4 for a range of scores 0-56 with higher scores indicating greater apathy. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORDaniel Lench
Medical University of South Carolina
Outcome results
None listed