Noninvasive Cortical Stimulation to Improve Memory in Mild Cognitive Impairment
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 69
- 试验地点
- 2
- 主要终点
- Total Number of Words Correctly Recalled, List Learning, California Verbal Learning Test-II, Assessed 1 Week After Intervention and Adjusted for Baseline Performance
研究概览
简要总结
The goal of this study is to test the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) as a treatment for Mild Cognitive Impairment (MCI). Participants will be randomly assigned to one of three treatment groups: Group 1: Active Dorsolateral Prefrontal Cortex (DLPFC) rTMS; Group 2: Active Lateral Parietal Cortex (LPC) rTMS; and Group 3: Inactive rTMS (Placebo) control (evenly split between each coil location). Participation in the study takes approximately 7 ½ months-including a 2-to 4-week treatment phase (20 rTMS sessions) and a 6-month follow-up phase.
详细描述
This study aims to test the efficacy of a non-pharmacological treatment for MCI that involves noninvasive brain stimulation (NIBS). Early studies in Alzheimer's disease (AD) dementia patients have found that repetitive transcranial magnetic stimulation (rTMS, a form of NIBS) improved global cognitive function and activities of daily living. Given that in AD, neuronal loss and synaptic dysfunction progress along brain networks, the results of these early studies of brain stimulation suggest there is sufficient neuroplasticity in AD for efficacious effects of brain stimulation. Of the very few rTMS studies in MCI that have been published, the effect size appears to be moderately large. However, it is not clear whether the dorsolateral prefrontal cortex (DLPFC), the stimulation site used in the most of the prior MCI/AD rTMS trials, is the optimal site for achieving the most efficacious effects including effects on episodic memory. Importantly, when other investigators used rTMS to stimulate a lateral parietal cortical (LPC) site in healthy young adults, significant effects of rTMS on memory were measureable weeks later. Moreover, functional connectivity of brain regions was selectively increased, including the posterior cingulate cortex (PCC), a "hub" of brain networks that is affected in amnestic MCI.
Because stimulation of the DLPFC and the LPC may each have distinct effects, we designed this pilot trial to have two active rTMS treatment groups: DLPFC and LPC. A third group will receive inactive (placebo) rTMS to achieve a controlled, randomized, double-blind trial. For each of the three groups, stimulation will be bilateral, based on effects achieved in the AD studies. The primary hypothesis is that active rTMS (to either site of stimulation) will be superior to inactive (placebo) rTMS in improving memory. Measures of change in functional connectivity will be computed to examine whether there is evidence that rTMS changes connectivity of the PCC with other regions of the brain. In addition to looking at effects of rTMS on functional connectivity and cognition in relation to the cortical site stimulated, genetic markers will be collected toward addressing heterogeneity of response. To track the durability of rTMS effects on memory, participants will be followed longer than in any prior study (up to 6 months after the intervention). If this study finds rTMS improves memory in older adults with MCI, further clinical development of this non-pharmacological treatment could ultimately improve the lives of millions of older adults who have MCI and are at an increased risk of developing dementia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 55 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with amnestic Mild Cognitive Impairment (aMCI);
- •Stable medications (including any dementia-related meds) for at least 4 weeks prior to Baseline;
- •Geriatric Depression Scale score less than 6;
- •Ability to obtain a motor threshold, determined during the screening process;
- •Study partner available; living situation enables attendance at clinic visits;
- •Visual and auditory acuity adequate for neuropsychological testing;
- •Good general health with no diseases expected to interfere with the study;
- •Participant is not pregnant or of childbearing potential (i.e. women must be 2 years post-menopausal or surgically sterile);
- •Modified Hachinski Ischemic score less than or equal to 4;
- •Agree to DNA extraction for single nucleotide polymorphism (SNP) genotyping;
- •Able to understand study procedures and comply with them for the entire length of the study.
排除标准
- •Prior exposure to rTMS within the past 12 months;
- •Magnetic field safety concern such as a cardiac pacemaker, cochlear implant, implanted device in the brain (deep brain stimulation), or metal fragments or foreign objects in the eyes, skin or body;
- •Any significant neurological disease other than suspected incipient Alzheimer's disease;
- •Unstable cardiac disease or recent (< 3 months previous) myocardial infarction. Any significant systemic illness or unstable medical condition that could lead to difficulty with protocol adherence;
- •History of epilepsy or repetitive seizures, as determined by patient report or chart review;
- •History of a medical condition or current use/abuse of medications and substances that increase the risk of a seizure, specifically:
- •Traumatic brain injury within 2 months that would increase the risk for seizure;
- •Unable to safely withdraw, at least 4 weeks prior to Baseline, from medications that substantially increase the risk of having seizures (for example: theophylline, clozapine, and methylphenidate).
- •Current or past history of a mass lesion, cerebral infarct, or other noncognitive active neurological disease that would increase the risk for seizure.
- •Stimulant abuse within the previous 90 days. Cocaine and abuse of amphetamine and methylphenidate are associated with an increased risk of seizures;
- •Major depression or bipolar disorder (DSM-IV) within the past 1 year, or psychotic features within the last 3 months that could lead to difficulty with protocol adherence;
- •Taking sedative hypnotics or medications with anti-cholinergic properties and unable to withdraw at least 4 weeks prior to Baseline;
- •Current alcohol or substance abuse (not including caffeine or nicotine) within the past 1 year, as determined by chart review, participant or study partner report, or greater than "moderate" alcohol use defined by the Quantity-Frequency-Variability Index (Cahalan, Cisin, & Crossley, 1969);
- •Any contraindications for magnetic resonance imaging (MRI) studies, e.g. severe claustrophobia, weight above 350 lb maximum allowed by MRI scanner, pregnancy;
- •Participation in another concurrent clinical trial;
- •Inability or unwillingness of individual or legal representative to give written informed consent.
结局指标
主要结局
Total Number of Words Correctly Recalled, List Learning, California Verbal Learning Test-II, Assessed 1 Week After Intervention and Adjusted for Baseline Performance
时间窗: 1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.
The California Verbal Learning Test, Second edition (CVLT-II) is a memory task that yields several indices of the ability to learn a list of semantically related words and remember the list after a delay interval. The target list ("List A") of the CVLT-II contains 16 words. There are 5 orally presented learning trials; each is followed by immediate recall of the words in any order. The total number of words correctly recalled on the 5 list-learning trials was computed (range = 0 to 80). Higher values represent a better outcome.
次要结局
- Total Number of Words Correctly Recalled, List Learning, California Verbal Learning Test-II, Assessed 3 Months After Intervention and Adjusted for Baseline Performance(3 months after completing the 20-session intervention (acceptable window for assessment: 76-104 days after the final intervention session))
- California Verbal Learning Test-II (CVLT-II) Semantic Clustering Score, 1 Week After Intervention and Adjusted for Baseline Performance(1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.)
- Total Number of Words Correctly Recalled During the "Long Delay Free Recall" Component of the California Verbal Learning Test-II (CVLT-II), Assessed 1 Week After Intervention and Adjusted for Baseline Performance(1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention)
- Depressive Symptoms, as Measured by the Geriatric Depression Scale (GDS), Assessed 1 Week After Intervention and Adjusted for Baseline Performance(1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.)
- Everyday Functional Outcomes, as Measured by the Everyday Cognition (ECog) Questionnaire (Participant Version) Completed 1 Week After Intervention(1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention)
- Everyday Functional Outcomes, as Measured by the Everyday Cognition Questionnaire (Informant /Study Partner Version) Completed 1 Week After Intervention(1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention)
- Instrumental Activities of Daily Living (IADLs), as Measured by the Functional Assessment Questionnaire, Completed 1 Week After Intervention(1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.)
- Global Cognitive Function, as Measured by the Montreal Cognitive Assessment (MoCA), Assessed 1 Week After Intervention and Adjusted for Baseline(1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention)
- Visuospatial Memory, as Measured by the Brief Visuospatial Memory Test-Revised (BVMT-R), assessed1 Week After Intervention and Adjusted for Baseline Performance(1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.)
- Language Function, as Measured by Category Fluency (CF), Assessed 1 Week After Intervention and Adjusted for Baseline Performance(1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.)
- Language Function, as Measured by 42-item Boston Naming Test (BNT), Assessed 1 Week After Intervention and Adjusted for Baseline Performance(1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.)
- Visuoconstructional Function, as Measured by the Rey-Osterrieth Complex Figure (ROCF) Copy Score, assessed1 Week After Intervention and Adjusted for Baseline Performance.(1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.)
- Speed of Processing and Executive Function, as Measured by Trail Making Part B, Assessed 1 Week After Intervention and Adjusted for Baseline Performance(1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.)
- Attention, as Measured by the Attentional Network Task (ANT), Assessed 1 Week After Intervention and Adjusted for Baseline Performance(planned: 1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.)
- Change From Baseline in Brain Functional Connectivity(planned: 1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.)
- Pre-post Change in Peripheral Levels of Brain-derived Neurotrophic Factor (BDNF)(First Intervention session to Last Intervention session. The average time frame from the first to the 20th and last session is 18 days.)
研究者
Joy Taylor
Principal Investigator
Palo Alto Veterans Institute for Research