Accelerated Intermittent Theta Burst Stimulation for Mild Cognitive Impairment in Parkinson's Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Serious Adverse Events
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Accelerated iTBS
Participants will undergo accelerated intermittent theta burst stimulation (iTBS) targeting the right superior parietal lobule (rSPL) using a MagVenture MagPro system with a cooled butterfly coil, with Brainsight neuronavigation identifying the stimulation site. Resting motor threshold (rMT) will be determined on the first stimulation visit using Parameter Estimation by Sequential Testing (PEST). Stimulation for the intervention will be delivered at 120% rMT. Stimulation sessions will occur over three consecutive days. Each day will include 10 sessions separated by 10-15 min. Each session delivers 600 pulses (50 Hz triplets; 2 s on/8 s off; ~190 seconds), totaling 6,000 pulses/day and 18,000 pulses overall. Coil position/angle and scalp-to-cortex distance are tracked; tolerability/acceptability (headache, pain, scalp irritation, facial twitching, fatigue, fear/anxiety) will be assessed before and after sessions.
干预措施: Accelerated intermittent theta-burst stimulation (iTBS) rTMS to right superior parietal lobule (rSPL) (Device)
结局指标
主要结局
Serious Adverse Events
时间窗: Week 4, 5 minutes before and 5 minutes after stimulation sessions on Days 1-3
Number of serious adverse events experienced by study participants caused by the iTBS protocol
Feasibility of the study protocol
时间窗: Week 0 through completion of study (8 weeks)
Feasibility will be defined as the proportion of participants enrolled that complete all intervention procedures
Tolerability of TMS procedures
时间窗: Week 4, 5 minutes before and 5 minutes after stimulation sessions on Days 1-3
A questionnaire evaluating the presence and severity of commonly experienced side effects of TMS (i.e. headache, pain, scalp irritation, facial twitching, fatigue, fear/anxiety) within the past 24 hours and during stimulation. Ratings will be on a 6-point Likert scale from 0 (no symptoms) to 5 (severe symptoms).
Test-retest reliability of the Continuous Temporal Expectancy Test (CTET)
时间窗: Week 0 (4 weeks pre-intervention) to Week 4, Day 1 (30 minutes prior to intervention)
The CTET is a tablet-administered measure designed to assess sustained attention and distractibility. Participants will be shown a grid with black and white squares on a tablet that rotate after either a longer duration (target stimulus; 1070ms) or a shorter duration (non-target stimulus; 800ms) and must press the screen when they identify a target stimulus. Participants will complete 10 one-minute trials. Half of the trials are performed without a distractor present, and the other half are performed with an audio-video distractor presented on an adjacent laptop screen. The primary outcome is the distractibility score, defined as the difference in latency (in ms) to identifying the target stimulus between distractor and non-distractor trials.
次要结局
- Change in Continuous Temporal Expectancy Task (CTET) Distractibility Score(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(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(Week 0 (1 month pre-intervention) to Week 8 (1 month post-intervention))
- Change in Beck Depression Inventory II (BDI-II) Raw Score(Week 4, Day 1 (pre-intervention) to Week 8 (1 month post-intervention))
- Change in Beck Anxiety Inventory (BAI) Score(Week 1, Day 1 (pre-intervention) to Week 8 (one-month follow-up))
- Change in Apathy Evaluation Scale (AES) Raw Score(Week 4, Day 1 (pre-intervention) to Week 8 (1-month post-intervention))
研究者
Sam Crowley
Assistant Professor-Faculty
Medical University of South Carolina