The Wandering Nerve: Gateway to Boost Alzheimer's Disease Related Cognitive
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 126
- 试验地点
- 1
- 主要终点
- Being a responder as determined by Face-name association memory task (FNAME) change scores
研究概览
简要总结
In this research study the investigators want to find out if a non-invasive electrical brain stimulation method called RAVANS (also called tVNS) can have a beneficial effect on cognition in older individuals. The investigators also want to understand whether certain individual factors contribute to the effect of RAVANS on cognition. RAVANS is only used in research studies.
详细描述
The intervention will be studied in 140* older individuals using a randomized cross-over design of sham versus RAVANS stimulation (2 sessions separated by 4 weeks) during a functional magnetic resonance imaging (fMRI) task. Participants will then be randomized to daily tVNS or sham sessions during 10 visits within two weeks, and two follow-up cognitive assessments each after 2 months of the last intervention session. The face-name association task will be the main outcome measure. The investigators will also draw blood twice to examine whether the response on the outcome is dependent on Alzheimer's disease related biomarker, and whether RAVANS has effects on inflammatory responses.
* Please note that the target accrual was revised to N = 126 due lower than expected drop-out rates. This change was approved by the Mass General Brigham IRB, DSMB, and NIH.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- Single (Participant)
盲法说明
Participant will not be informed of condition. The investigators will work with blinded data (but can know the condition during intervention)
入排标准
- 年龄范围
- 60 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Fluent in English
- •Willingness and ability to comply with scheduled visits, magnetic resonance imaging (MRI) scanning, laboratory tests, and other study procedures.
- •Subjects with well-controlled vascular risk factors, such as treated hypertension, treated hyperlipidemia or well controlled Type II diabetes will be included.
- •Stable medications for at least 30 days.
- •Mini Mental State Exam adjusted for age and education of 25 to 30, inclusive or a Telephone Interview for Cognitive Status score of at least 32
- •Perform within 1.5 S.D. of age and education matched norms on the Logical Memory Paragraph Delayed Recall
- •Geriatric Depression Scale < 11
- •Aged 60-85, inclusive
- •Right-handed
- •Reduced vision is allowed if it can be corrected with MRI-goggles
排除标准
- •Prior known diagnosis of mild cognitive impairment (MCI) or dementia
- •Use of investigational drugs or devices within 60 days prior to screening
- •Subjects with contraindications to MRI cannot participate (i.e., implanted metal including pacemakers, cerebral spinal fluid shunts, aneurysm clips, artificial heart valves, ear implants or metal/foreign objects in the eyes and those with a history of claustrophobia)
- •Pregnant.
- •Major psychiatric disorders such as schizophrenia, schizoaffective disorder, major affective disorder in mid-life, or treatment with electroconvulsive therapy (ECT) (Mild depression that is well treated with stable dose of selective serotonergic reuptake inhibitor (SSRI) antidepressants will be allowed).
- •Have a history of major head trauma defined as a loss of consciousness and/or trauma requiring hospitalization
- •Substance abuse within the past 2 years
- •Active hematological, renal, pulmonary, endocrine or hepatic disorders.
- •Evidence of cortical infarcts or strategically placed lacunar infarct (e.g. dorsal medial nucleus of thalamus). MRI evidence of mild white matter signal abnormalities will be allowed.
- •Active cancer, metabolic encephalopathy, infection
- •Active cardiovascular disease, stroke, congestive or severe heart failure
- •Huntington's disease, hydrocephalus or seizure disorder
- •Cataracts, glaucoma, detached retina's, eye surgery involving the muscles; droopy eyelids, penetrating eye wounds and use of anticholinergic eye drop use
- •Weight equal to or greater than 300 lbs (weight limit of the MRI table).
- •Recurrent vaso-vagal syncopal episodes
- •Unilateral or bilateral vagotomy
- •Severe valvular disorder (i.e. prosthetic valve or hemodynamically relevant valvular diseases)
- •Sick sinus syndrome
- •Hypotension due to autonomic dysfunction
研究组 & 干预措施
Stimulation preceded by cross-over Stimulation-Sham
Cross-over: experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) followed by sham Wash-out period of four weeks Ten daily sessions of RAVANS during 2 weeks
干预措施: Active transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions (Other)
Sham preceded by cross-over Stimulation-Sham
Cross-over: experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) followed by Sham Wash-out period of four weeks Ten daily sessions of sham during 2 weeks
干预措施: Sham transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions (Other)
Stimulation preceded by cross-over Sham-Stimulation
Cross-over: Sham followed by experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) Wash-out period of four weeks Ten daily sessions of RAVANS during 2 weeks
干预措施: Active transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions (Other)
cross-over Stimulation-Sham
Cross-over: experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) followed by sham One time RAVANS versus one time Sham Two weeks wash-out
干预措施: Active transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions (Other)
cross-over Stimulation-Sham
Cross-over: experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) followed by sham One time RAVANS versus one time Sham Two weeks wash-out
干预措施: Sham transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions (Other)
cross-over Sham-Stimulation
Cross-over: Sham followed by experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) One time RAVANS versus one time Sham Two weeks wash-out
干预措施: Active transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions (Other)
cross-over Sham-Stimulation
Cross-over: Sham followed by experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) One time RAVANS versus one time Sham Two weeks wash-out
干预措施: Sham transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions (Other)
Sham preceded by cross-over Sham-Stimulation
Cross-over: Sham followed by experimental Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) Wash-out period of four weeks Ten daily sessions of sham during 2 weeks
干预措施: Sham transcutaneous vagus nerve stimulation respiratory-gated non-painful electrical stimulation of the auricle for 10 minute sessions (Other)
结局指标
主要结局
Being a responder as determined by Face-name association memory task (FNAME) change scores
时间窗: Based on data from the first 4 weeks (cross-over)
Participants are grouped in being a responder (1) or non-responder (0).
Performance on the Face-name association memory task (FNAME)
时间窗: Up to 25 weeks: assessed during week 1, week 2, week 8,week 9, week 17 and week 25
Change from baseline at each visit where FNAME is completed: Scores are z-scores with a mean of zero. Higher scores are better (there is no minimum/maximum).
次要结局
- Performance on other cognitive composite scores: this includes a composite score of memory, a composite score of executive function and the Preclinical Alzheimer's disease cognitive composite.(Up to 25 weeks: assessed during week 1, week 2, week 8,week 9, week 17 and week 25)
- Change in inflammatory responses (MCP)(Assessed during the first week and during week 9)
- Change in inflammatory responses (aggregated)(Assessed during the first week and during week 9)
- Change in inflammatory responses (interleukins)(Assessed during the first week and during week 9)
- Change in inflammatory responses (TNF)(Assessed during the first week and during week 9)
- Change in inflammatory responses (MIP)(Assessed during the first week and during week 9)
- Change in inflammatory responses (C)(Assessed during the first week and during week 9)
- Change in inflammatory responses (TREM)(Assessed during the first week and during week 9)
研究者
Heidi Jacobs
Associate Professor of Radiology
Massachusetts General Hospital