Modulation of Hippocampal Circuitry and Memory Function With Focused Ultrasound in Amnestic MCI
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 120
- 试验地点
- 3
- 主要终点
- Change in Perfusion Arterial Spin Labeling (ASL) fMRI Signal throughout Brain
研究概览
简要总结
The goal of this study is to investigate whether Low Intensity Focused Ultrasound Pulsation (LIFUP) targeting a part of the brain involved in memory will have an affect on brain activity and whether it may improve memory in people with Mild Cognitive Impairment and Mild Alzheimer's Disease.
The main questions the study seeks to answer are:
- Can LIFUP increase brain activity in the targeted area?
- Can LIFUP improve memory in people with MCI and mild AD?
- Can LIFUP improve connectivity of memory networks in the brain?
Participants in this study will complete MRIs and memory testing, and receive Low Intensity Focused Ultrasound to a part of their brain involved in memory (the entorhinal cortex).
详细描述
This is a proof of concept trial of Low Intensity Focused Ultrasound Pulsation (LIFUP) targeting the entorhinal cortex in patients with amnestic MCI and Mild Alzheimer's Disease. Participation in the study will entail one Zoom intake session, three in-person sessions and three remote Zoom follow-up sessions over the course of about five weeks. The in-person sessions will take about 5 hours for the first and 3 hours for the following two. The Zoom intake session will take 1-2 hours, and the Zoom follow-up sessions will take about 2 hours each. Participants will be asked to complete questionnaires and tests of learning and memory, have their blood drawn, undergo painless ultrasound stimulation to a part of their brain related to memory, and complete MRI scans of their brain. LIFUP will be administered inside of the MRI scanner, so that we can measure changes in brain activity in real-time.
At the start of the study, you will be randomly assigned to one of four different groups that determines the amount of LIFUP stimulation you will receive. You have an equal chance of being assigned to each group. Participants in one of the three active stimulation groups will receive either 1 dose, 2 doses, or 3 doses of LIFUP at their second in-person session, and will receive the same dose again at their third in-person session. Participants in the placebo group will receive no LIFUP stimulation at either MRI/LIFUP session (in-person visits 2 and 3). However, if at the end of our study, the treatment has been shown to be effective, and you were a placebo subject, we will offer you a free session using the most effective dose.
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
- Double (Participant, Outcomes Assessor)
盲法说明
Participants and the participants' caregivers will be blinded to arm assignment. Additionally, the person administering memory testing will be blinded to assignment.
入排标准
- 年龄范围
- 50 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Amnestic MCI or Mild Alzheimer's diagnosis
- •Age 50-90
- •English-speaking
- •Ability to provide informed consent
- •Normal or corrected-to-normal hearing and vision
排除标准
- •Participation in another clinical trial
- •Active use of immunotherapeutic medications for cognition (Aduhelm, Leqembi, Kisunla)
- •Moderate to Severe Alzheimer's
- •Inability to provide informed consent
- •MRI-Related:
- •Weight exceeding 275 pounds
- •Pregnancy, suspicion of pregnancy, or attempting to become pregnant
- •Claustrophobia
- •Difficulties during previous MRIs
- •Top permanent retainer (bottom only is okay), 5 or more non-removable gold-teeth, metal braces, top spacers, and/or palate expanders
- •Any of the following implants: Cardiac Pacemaker, Aneurysm clips, Cochlear implants, Defibrillator, Electrodes or wires, Magnetically-activated device, Spinal cord stimulator, Infusion or insulin pumps, Implanted drug infusion device, Deep brain stimulation device
- •Non-removable hairpieces, hairpiece extensions, and/or piercings
- •Facial tattoos or permanent makeup
- •Metal implants that are MR-incompatible, or where participant is unable to provide sufficient information to determine MR compatibility
- •Previous injury by metallic foreign body (e.g., bullet, BB, shrapnel) where the object entered the body and participant lacks doctor's confirmation that it was fully removed
- •Diagnosis of one or more of the following neurological disorders: Parkinson's disease, Lou Gehrig's disease (ALS), Multiple sclerosis, Cerebral Palsy
- •Diagnosis of one or more of the following genetic disorders: Cystic Fibrosis, Sickle Cell Disease
- •Diagnosis of one or more of the following psychiatric disorders: Bipolar, Psychosis
- •Psychiatric illness that has not been controlled for at least two months (if controlled >2 months, with or without medication, they are not exclusionary)
- •Severe lung, liver, heart, and/or kidney disease/s (e.g., heart failure, liver failure, and etc...)
- •Diagnosis of thyroid disorder or change of thyroid medication dose within the last 3 months
- •Cancer treatment/s with chemotherapy and/or radiation to head and neck, or stage 4 (metastatic) cancer
- •Autoimmune disorder or viral infection such as HIV, COVID 19, or hepatitis C that has caused current problems with cognition/memory
- •History of substance abuse in the past year
- •History of stroke (Transient ischemic attack / mini-stroke not exclusionary if symptoms lasted <1 week)
- •History of 2 or more seizures or diagnosis of epilepsy, unless the seizures occurred prior to age 5 alongside a fever.
- •History of brain tumor, brain aneurysm, brain hemorrhage, or subdural hematoma (transient ischemic attack not exclusionary)
- •Head injury that resulted in loss of consciousness lasting >30 minutes, cognitive issues lasting >18 months, and/or brain abnormalities visible in CT or MRI scan
- •Uncontrolled high blood pressure or diabetes
- •Heart attack within the last year
研究组 & 干预措施
Sham LIFUP
No administration of LIFUP. The device will be affixed to the user's head but not turned on.
Additionally, if at the end of the study, the treatment has been shown to be effective, placebo subjects will be offered a free session using the optimally effective dose, if they consented to being contacted for this purpose.
干预措施: Low-Intensity Focused Ultrasound Pulsation (LIFUP) (Device)
LIFUP Dose Group 1
Administration of low intensity focused ultrasound (LIFUP) dose level 1 to the entorhinal cortex.
干预措施: Low-Intensity Focused Ultrasound Pulsation (LIFUP) (Device)
LIFUP Dose Group 2
Administration of low intensity focused ultrasound (LIFUP) dose level 2 to the entorhinal cortex.
干预措施: Low-Intensity Focused Ultrasound Pulsation (LIFUP) (Device)
LIFUP Dose Group 3
Administration of low intensity focused ultrasound (LIFUP) dose level 3 to the entorhinal cortex.
干预措施: Low-Intensity Focused Ultrasound Pulsation (LIFUP) (Device)
结局指标
主要结局
Change in Perfusion Arterial Spin Labeling (ASL) fMRI Signal throughout Brain
时间窗: 40 minutes
Perfusion ASL fMRI data will be collected before and after sonication. Analyses will assess the statistical relationship between ASL signal throughout the brain pre and post sonication.
Changes in BOLD-related functional connectivity from baseline in fMRI brain scan to 40 minutes.
时间窗: 40 minutes
Primary outcomes for proof of mechanism that may be depicted in the fMRI scans may include changes in BOLD-related functional connectivity increases within the DMN including regions functionally connected to the target. BOLD data will be collected before, during, and following LIFUP sonication. Analyses will assess any changes in BOLD signal in the brain following sonication.
次要结局
- Post-hoc biomarker analysis of plasma AB42/40 ratio as a predictor of tFUS efficacy(Baseline (pre-LIFUP))
- Change in Brief Visual Memory Test Scores(48 hours)
- Change in Verbal Learning Test Scores(48 hours)
- Post-hoc biomarker analysis of plasma ptau as a predictor of tFUS efficacy(Baseline (pre-LIFUP))
- Post-hoc biomarker analysis of APOE-4 status as a predictor of tFUS efficacy(Baseline (pre-LIFUP))
研究者
Susan Bookheimer, PhD
Principal Investigator
University of California, Los Angeles