Superior Parietal iTBS for PD-MCI

Official title

Accelerated Intermittent Theta Burst Stimulation for Mild Cognitive Impairment in Parkinson's Disease

Overview

The goal of this study is to determine the whether a short-term, high-dose form of non-invasive brain stimulation (intermittent theta burst stimulation; iTBS) is a promising and safe treatment for mild cognitive impairment in Parkinson's disease (PD-MCI).

Detailed description

Dementia occurs in 80% of people with Parkinson's disease (PD) within 20 years of diagnosis. Cognitive interventions in PD have centered on individuals with mild cognitive impairment (PD-MCI). A lack of efficacy of pharmacological interventions in PD-MCI has driven interest in nonpharmacological approaches. The most promising of these is intermittent theta burst stimulation (iTBS), a noninvasive brain stimulation method that is FDA-approved for several psychiatric conditions. Though iTBS has shown little to no benefit in PD-MCI thus far, there are modifiable issues with past interventions including exclusively targeting prefrontal cortex when cholinergic denervation in posterior cortex is strongly associated with cognitive decline in PD, and substantial underdosing compared to efficacious iTBS interventions (6,000 vs at least 18,000 pulses). Interventions will likely have better outcomes if they target the right superior parietal lobule (rSPL), a cortical region impacted by cholinergic denervation in PD that is essential to maintaining attention, and use accelerated iTBS (a-iTBS) to deliver a stimulation dose commensurate with FDA-approved protocols in a shorter timeframe. However, before the efficacy of such an intervention can be evaluated, it must be established as safe, tolerable and feasible in PD-MCI. This project therefore aims to evaluate the safety, tolerability and feasibility of a three-day a-iTBS intervention stimulating the rSPL with 18,000 total pulses.

Interventions

• Device Accelerated intermittent theta-burst stimulation (iTBS) rTMS to right superior parietal lobule (rSPL)
  Participants in this single-arm study will receive a accelerated course of intermittent theta burst stimulation (iTBS) over superior parietal lobule, which is identified with MNI coordinates from past studies. The stimulation will be delivered using a MagVenture MagPro TMS System with a butterfly, active cooling coil at 120% of resting motor threshold. Each participant will complete 3 consecutive treatment days, undergoing10 rTMS sessions per day (600 pulses/session), totaling 18,000 pulses acr

Primary outcome measures

• Serious Adverse Events [Time frame: Week 4, 5 minutes before and 5 minutes after stimulation sessions on Days 1-3]
• Feasibility of the study protocol [Time frame: Week 0 through completion of study (8 weeks)]
• Tolerability of TMS procedures [Time frame: Week 4, 5 minutes before and 5 minutes after stimulation sessions on Days 1-3]
• Test-retest reliability of the Continuous Temporal Expectancy Test (CTET) [Time frame: Week 0 (4 weeks pre-intervention) to Week 4, Day 1 (30 minutes prior to intervention)]

Secondary outcome measures (6)

• Change in Continuous Temporal Expectancy Task (CTET) Distractibility Score [Time frame: Week 4, Day 1 (30 minutes prior to intervention) to Week 4, Day 3 (15 minutes after intervention) to Week 8 (4 weeks post-intervention)]
• Change in NIH Toolbox Cognitive Battery (NIHTB-CB) Composite Scores [Time frame: Week 4, Day 1 (30 minutes prior to intervention intervention) to Week 4, Day 3 (15 minutes after intervention) to Week 8 (4 weeks post-intervention)]
• Change in daily functioning [Time frame: Week 0 (1 month pre-intervention) to Week 8 (1 month post-intervention)]
• Change in Beck Depression Inventory II (BDI-II) Raw Score [Time frame: Week 4, Day 1 (pre-intervention) to Week 8 (1 month post-intervention)]
• Change in Beck Anxiety Inventory (BAI) Score [Time frame: Week 1, Day 1 (pre-intervention) to Week 8 (one-month follow-up)]
• Change in Apathy Evaluation Scale (AES) Raw Score [Time frame: Week 4, Day 1 (pre-intervention) to Week 8 (1-month post-intervention)]

Eligibility criteria

Inclusion criteria

• 50-85 years of age
• Diagnosis of Parkinson's disease based on UK Brain Bank diagnostic criteria
• Parkinson's disease with mild cognitive impairment (PD-MCI) diagnosis per Movement Disorders Society Task Force Level II Diagnostic Criteria4 (i.e., scores ≥1.5 standard deviations below appropriate norms on 2 neuropsychological tests) as determined by a clinical neuropsychologist
• Stable on Parkinson's disease medications for 30 days (not expected to change through the course of the treatment)
• Has a caregiver willing and able to reliably complete a questionnaire focused on the participant's daily functioning

Exclusion criteria

• Claustrophobia or inability to lie supine in the scanner for an extended period of time
• Barriers to making contact between the TMS coil and the skin (e.g. braids that cannot be removed)
• Contraindications to MRI/TMS safety screening: This includes but is not limited to implanted medical devices (e.g., pacemakers), metallic objects or fragments, non-removable hair clips or piercings, and medications that reduce seizure threshold.
• Individuals with a diagnosis of bipolar disorder, schizophrenia, and/or active substance abuse disorder.
• History of significant or unstable condition/s or treatments for these condition/s that may impact cognition (as determined by the study investigators) such as significant cardiac (e.g. heart failure), infectious (e.g. HIV, urinary tract infection), or metabolic disease (e.g. labile diabetes), cancer (e.g. brain cancer, chemotherapy-induced cognitive impairment), developmental disorder (e.g. autism spectrum disorder, intellectual disability), or other neurologic disease (e.g. multiple sclerosis, moderate to severe brain injury, seizures).
• History of a seizure disorder.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Medical University of South Carolina — Charleston

Identifiers

NCT: NCT07701785 · Pro00151225 · K12TR005297

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗