Low-Intensity Focused Ultrasound (LIFU) Neuromodulation

Study Overview
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Brief Summary
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This study is a prospective, single-center, single-arm early feasibility study, to establish safety and tolerability of LIFU for neuromodulation in patients with mild cognitive impairment ( MCI) due to Alzheimer's disease.

Detailed Description
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The primary objective is to evaluate the safety, feasibility and tolerability of LIFU as an adjunct neuromodulatory treatment for MCI due to AD

Official Title
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Early Feasibility Study of Low-Intensity Focused Ultrasound (LIFU) Neuromodulation in Patients With Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Device: low intensity focused ultrasound (LIFU)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and non-pregnant females, aged 45-85 years Able and willing to give informed consent Must meet the clinical criteria for MCI due to Alzheimer's disease If receiving concurrent treatment with an AChEI and/or memantine, has been on a stable dose for at least 45 days Able to communicate sensations during the LIFU procedure Exclusion Criteria: Unable to undergo MR-imaging because of implanted pacemakers, medication pumps, aneurysm clips, metallic prostheses (including metal pins and rods, heart valves or cochlear implants), shrapnel fragments, permanent make-up or small metal fragments in the eye that welders and other metal workers may have, or if candidates are uncomfortable in small spaces (have claustrophobia). Participants with more than 30% of the skull area traversed by the sonication pathway are covered by scars, scalp disorders (e.g., eczema), atrophy of the scalp, or implanted objects in the skull or the brain. Participants with a history of seizure disorder. Participants with clinically significant chronic pulmonary disorders e.g., severe emphysema, pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area. Participant does not speak English Participant is pregnant or planning to be pregnant

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neuromodulation<br>Subjects meeting eligibility criteria will undergo Exablate low intensity focused ultrasound neuromodulation | Device: low intensity focused ultrasound (LIFU)<br>* Subjects will undergo undergo a single LIFU of the target brain region<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Treatment Emergent Adverse Events | Safety will be assessed by recording all adverse events that are treatment related. Each Adverse Event will be documented for patterns of occurence. | baseline and 7 and days after study procedure | 
| Cognitive Change | Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) | baseline and 7 days after procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Imaging Changes | Changes in brain metabolism and connectivity using PET and fMRI | baseline, 7 and 30 days |