Low Intensity Focused Ultrasound for Mild Cognitive Impairment and Mild Alzheimer's Disease (LIFUP-MCIAD)

University of California, Los Angeles (UCLA)

Status: Enrolling

Conditions: Mild Alzheimer's Disease; Amnestic Mild Cognitive Disorder; Mild Cognitive Impairment; Deep Brain Stimulation

Treatments: Device: Low-Intensity Focused Ultrasound Pulsation (LIFUP)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05417555

IRB#21-000995 (Other Identifier)

Details and patient eligibility

About

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:

1. Can LIFUP increase brain activity in the targeted area?
2. Can LIFUP improve memory in people with MCI and mild AD?
3. 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).

Full description

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.

Enrollment: 144 estimated patients

Sex: All

Ages: 50 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• 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

Exclusion Criteria

GENERAL

• 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

Medical:

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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144 participants in 4 patient groups

LIFUP Dose Group 1

Active Comparator group

Description:

Administration of low intensity focused ultrasound (LIFUP) dose level 1 to the entorhinal cortex.

Treatment:

Device: Low-Intensity Focused Ultrasound Pulsation (LIFUP)

LIFUP Dose Group 2

Active Comparator group

Description:

Administration of low intensity focused ultrasound (LIFUP) dose level 2 to the entorhinal cortex.

Treatment:

Device: Low-Intensity Focused Ultrasound Pulsation (LIFUP)

LIFUP Dose Group 3

Active Comparator group

Description:

Administration of low intensity focused ultrasound (LIFUP) dose level 3 to the entorhinal cortex.

Treatment:

Device: Low-Intensity Focused Ultrasound Pulsation (LIFUP)

Sham LIFUP

Sham Comparator group

Description:

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.

Treatment:

Device: Low-Intensity Focused Ultrasound Pulsation (LIFUP)