Transcranial Pulse Stimulation of the Brain in Older Adults With and Without Mild Dementia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- ADAS-Cog-Plus-EF&FA Battery Total Score
研究概览
简要总结
This study will investigate transcranial pulse stimulation (TPS) as a method of enhancing cognitive and neural function. The study team will apply this low intensity, magnetically pulse technology to key brain regions in a randomized, sham-controlled trial (RCT). The study will determine the magnitude of changes in cognitive function and brain function and structure between a pre- and post-stimulation among 10 typically-aging older adults and 10 patients with mild dementia.
详细描述
The current study will investigate the use of the NEUROLITH TPS (transcranial pulse stimulation) generator device (Storz Medical AG, Tägerwilen, Switzerland) for enhancing cognitive and neural function in older adults with and without mild Alzheimer's disease (AD). This will be achieved by applying a novel, low intensity, magnetically pulsed technology to key brain regions and networks in a randomized, sham-controlled trial (RCT). The pilot RCT will be conducted to determine the magnitude of changes in cognitive function and brain function and structure between a pre- and post-stimulation using a 2x2 sham-controlled design in which 10 typically-aging older adults and 10 patients with mild AD will be randomized to receive either sham TPS or active TPS. All participants will undergo pre-intervention multi-modal MRI, blood draw, and neurocognitive evaluation followed by thrice-weekly TPS (sham or active) for two weeks total, followed by a post-intervention MRI, blood draw, and neurocognitive evaluation. The total duration of the study is expected to be around four weeks, where each participant will undergo a screening/eligibility visit, baseline visit with MRI and neurocognitive testing, 6 intervention visits, a post-intervention MRI and neurocognitive testing visit after the final stimulation session for a total of about 9 in-person visits. The final week of the study is a no-contact period in which the participant will be called approximately seven days after their final stimulation session to ensure no adverse events have occurred. The team will also contact participants quarterly for one year after the final session to complete a five minute phone survey.
The central hypothesis of this proposal is that TPS will increase cortical thickness, cerebral blood flow, neurite orientation and dispersion, and functional connectivity in targeted regions and their associated networks. Further, we hypothesize that these changes will translate to improvements in neurocognitive function more than that seen in the sham intervention, which is likely to occur due to practice effects alone.
The objectives of this study are to:
Aim 1. Determine whether application of TPS is associated with neurocognitive improvement H1.1. For both typically-aging older adults and patients with mild AD, active TPS will result in greater neurocognitive gains than sham TPS on a primary outcome measure of global cognition obtained from the ADAS-Cog-plus battery.
H1.2. Neurocognitive gains on the recall memory measures in active TPS will be greater for patients with mild AD compared to typically-aging older adults.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
All parties involved will be blinded to the participant condition with the exception of 1) the interventionist applying the pulsed stimulation to the participant brain, as they will be required to ensure the TPS device is set to sham/active before application of the stimulation, and 2) the biostatistician who will randomize participants with sex-stratification
入排标准
- 年龄范围
- 65 Years 至 84 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women
- •Age: 65 to 84 years
- •English speaking
- •Physically mobile with no history of balance difficulties or major falls
- •For the typically-aging older adult group, phone screening performance on the TICS must be greater than or equal to 33 points, and cognitive performance of 26 points or greater on the MoCA and a Sum of Boxes score of 0 on the Clinical Dementia Rating scale administered to the participant's informant at the initial visit
- •For the Mild dementia group, phone screening performance on the TICS must be between 21 and 32 points, and subsequent cognitive performance of on the MoCA must be <23 with a CDR Sum of Boxes score between 4.5 and 9.0 as administered to the participants known informant at the initial visit.
排除标准
- •Neurological disorders unrelated to dementia / AD (e.g., Parkinson's disease, stroke, seizures, traumatic brain injury)
- •Evidence of greater-than-mild dementia/AD (based on informant CDR Sum of Boxes score greater than 9.0 or MoCA <10)
- •Past opportunistic brain infection
- •Major psychiatric illness (schizophrenia, intractable affective disorder, current substance dependence diagnosis or severe major depression and/or suicidality) or any history of agitation and/or delirium
- •Unstable (e.g., cancer other than basal cell skin) and chronic (e.g., diabetes mellitus) medical conditions
- •MRI contraindications (e.g., pregnancy, claustrophobia, metal implants that are contraindicated for MRI and TPS)
- •Physical impairment precluding motor response or lying still for one hour and inability to walk two blocks without stopping or without balance difficulties
- •Drug exclusions include those medications that are known to have cognitively sedating or altering effects as well medications with a strong anticholinergic burden or CNS effects. Participants should be stable on any recently altered medications/dosages for at least four weeks prior to beginning the study. Medications will be reviewed during the interview for the purpose of identification of contraindicated pharmacological agents with common cognitive side-effects
- •Other history of medical conditions that may increase risk of cerebrovascular events, including prior heart attack, cardiac arrhythmia such as atrial fibrillation
- •Hearing or vision deficits that will not allow for reliable standardized cognitive assessment; i.e. colorblindness, inability to hear through headphones (with or without hearing aids), macular degeneration or other significant diseases that cause severe loss of vision. If vision is corrected with lenses to appropriate levels, then participant will be eligible
- •Left-handedness and ambidextrousness, as these individuals have a higher percentage rate of atypical functional lateralization for brain functions, which would significantly interfere with interpretability of brain data
- •Hemophilia or other blood clotting disorders or thrombosis
- •Corticosteroid treatment within the last six weeks before the first treatment
研究组 & 干预措施
Active brain stimulation
These participants will receive focused TPS (pulsed stimulation) of the specified default mode network regions as specified in the detailed study description.
干预措施: Neurolith Transcranial Pulse Stimulation Active (Device)
Sham brain stimulation
These participants will also receive focused TPS (pulsed stimulation) of the specified default mode network regions as specified in the detailed study description, though the device will be set to "Sham" in a blinded fashion by the biostatistician by placing an air pouch in the device hand piece.
干预措施: Neurolith Transcranial Pulse Stimulation Sham (Device)
结局指标
主要结局
ADAS-Cog-Plus-EF&FA Battery Total Score
时间窗: Four weeks
The ADAS-Cog-Plus total score is touted as the gold standard measure for outcomes measurement following anti-dementia interventions18, allows for reliable longitudinal data collection, and provides coverage of cognitive domains including orientation, memory, language, and praxis.
次要结局
- NIH Examiner Total Score(Four weeks)