Low Intensity Focused Ultrasound for Mild Cognitive Impairment and Mild Alzheimer's Disease

NCT ID: NCT05417555

Last Updated: 2024-09-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

144 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-09-01

Study Completion Date

2026-07-31

Brief Summary

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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).

Detailed Description

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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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Subjects are randomly assigned to one of four treatment dosage conditions: 0, 1, 2 or 3 treatments at each MRI-LIFUP session. After 2 weeks, a second dose is administered with the same dosage level for each subject. Memory assessment occurs once at baseline and remotely after each treatment at the onset of the optimal time window (48 hours) for LIFUP-induced change based on prior data. Finally, after 2 weeks, memory is again assessed. Alternate forms are used for the primary outcome measures to avoid practice effects.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors
Participants and the participants' caregivers will be blinded to arm assignment. Additionally, the person administering memory testing will be blinded to assignment.

Study Groups

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LIFUP Dose Group 1

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

Group Type ACTIVE_COMPARATOR

Low-Intensity Focused Ultrasound Pulsation (LIFUP)

Intervention Type DEVICE

Low intensity focused ultrasound pulsation will be administered to the left entorhinal cortex at 650kHz, ispta.3 720mW/cm, pulse repetition frequency 100Hz, duty cycle 50%, duration 30s with 30s spacing between sonications, 6 sonications per dose (participants receive 0, 1, 2 or 3 doses depending on group assignment)

LIFUP Dose Group 2

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

Group Type ACTIVE_COMPARATOR

Low-Intensity Focused Ultrasound Pulsation (LIFUP)

Intervention Type DEVICE

Low intensity focused ultrasound pulsation will be administered to the left entorhinal cortex at 650kHz, ispta.3 720mW/cm, pulse repetition frequency 100Hz, duty cycle 50%, duration 30s with 30s spacing between sonications, 6 sonications per dose (participants receive 0, 1, 2 or 3 doses depending on group assignment)

LIFUP Dose Group 3

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

Group Type ACTIVE_COMPARATOR

Low-Intensity Focused Ultrasound Pulsation (LIFUP)

Intervention Type DEVICE

Low intensity focused ultrasound pulsation will be administered to the left entorhinal cortex at 650kHz, ispta.3 720mW/cm, pulse repetition frequency 100Hz, duty cycle 50%, duration 30s with 30s spacing between sonications, 6 sonications per dose (participants receive 0, 1, 2 or 3 doses depending on group assignment)

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.

Group Type SHAM_COMPARATOR

Low-Intensity Focused Ultrasound Pulsation (LIFUP)

Intervention Type DEVICE

Low intensity focused ultrasound pulsation will be administered to the left entorhinal cortex at 650kHz, ispta.3 720mW/cm, pulse repetition frequency 100Hz, duty cycle 50%, duration 30s with 30s spacing between sonications, 6 sonications per dose (participants receive 0, 1, 2 or 3 doses depending on group assignment)

Interventions

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Low-Intensity Focused Ultrasound Pulsation (LIFUP)

Low intensity focused ultrasound pulsation will be administered to the left entorhinal cortex at 650kHz, ispta.3 720mW/cm, pulse repetition frequency 100Hz, duty cycle 50%, duration 30s with 30s spacing between sonications, 6 sonications per dose (participants receive 0, 1, 2 or 3 doses depending on group assignment)

Intervention Type DEVICE

Other Intervention Names

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transcranial focused ultrasound tFUS LIFUP low intensity focused ultrasound

Eligibility Criteria

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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
Minimum Eligible Age

50 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

University of California, Los Angeles

OTHER

Sponsor Role lead

Responsible Party

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Taylor Kuhn

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Susan Y Bookheimer, PhD

Role: PRINCIPAL_INVESTIGATOR

UCLA Psychiatry & Biobehavioral Sciences

Taylor P Kuhn, PhD

Role: PRINCIPAL_INVESTIGATOR

UCLA Psychiatry & Biobehavioral Sciences

Locations

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UCLA Semel Institute for Neuroscience and Behavior

Los Angeles, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Natalie Rotstein

Role: CONTACT

‭(310) 794-0077‬

Sabrina Halavi

Role: CONTACT

‭(310) 794-0077‬

Facility Contacts

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Natalie Rotstein

Role: primary

3107940077

Sabrina Halavi

Role: backup

3107940077

Taylor P Kuhn, PhD

Role: backup

Susan Y Bookheimer, PhD

Role: backup

References

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Hescham S, Lim LW, Jahanshahi A, Blokland A, Temel Y. Deep brain stimulation in dementia-related disorders. Neurosci Biobehav Rev. 2013 Dec;37(10 Pt 2):2666-75. doi: 10.1016/j.neubiorev.2013.09.002. Epub 2013 Sep 20.

Reference Type BACKGROUND
PMID: 24060532 (View on PubMed)

Lin WT, Chen RC, Lu WW, Liu SH, Yang FY. Protective effects of low-intensity pulsed ultrasound on aluminum-induced cerebral damage in Alzheimer's disease rat model. Sci Rep. 2015 Apr 15;5:9671. doi: 10.1038/srep09671.

Reference Type BACKGROUND
PMID: 25873429 (View on PubMed)

Burgess A, Dubey S, Yeung S, Hough O, Eterman N, Aubert I, Hynynen K. Alzheimer disease in a mouse model: MR imaging-guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior. Radiology. 2014 Dec;273(3):736-45. doi: 10.1148/radiol.14140245. Epub 2014 Sep 15.

Reference Type BACKGROUND
PMID: 25222068 (View on PubMed)

Bystritsky A, Korb AS, Douglas PK, Cohen MS, Melega WP, Mulgaonkar AP, DeSalles A, Min BK, Yoo SS. A review of low-intensity focused ultrasound pulsation. Brain Stimul. 2011 Jul;4(3):125-36. doi: 10.1016/j.brs.2011.03.007. Epub 2011 Apr 1.

Reference Type BACKGROUND
PMID: 21777872 (View on PubMed)

Related Links

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Other Identifiers

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1R01AG073480-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB#21-000995

Identifier Type: OTHER

Identifier Source: secondary_id

IRB#21-000995

Identifier Type: -

Identifier Source: org_study_id

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