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

NCT05417555 | Recruiting DMC FDA Device

• 2 other identifiers: IRB#21-0009951R01AG073480-01
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Keywords

deep brain stimulation (DBS); transcranial focused ultrasound stimulation (tFUS); memory; low-intensity focused ultrasound pulsation (LIFUP); fMRI; mild cognitive impairment; mci; noninvasive brain stimulation (NIBS); ultrasound; Alzheimer's Disease; Mild Alzheimer's

Outcome Measures

Primary Outcomes (2)

• Change in Perfusion Arterial Spin Labeling (ASL) fMRI Signal throughout Brain

  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.

  40 minutes

• Changes in BOLD-related functional connectivity from baseline in fMRI brain scan to 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.

  40 minutes

Secondary Outcomes (5)

• Change in Brief Visual Memory Test Scores

  48 hours

• Change in Verbal Learning Test Scores

  48 hours

• Post-hoc biomarker analysis of APOE-4 status as a predictor of tFUS efficacy

  Baseline (pre-LIFUP)

• Post-hoc biomarker analysis of plasma AB42/40 ratio as a predictor of tFUS efficacy

  Baseline (pre-LIFUP)

• Post-hoc biomarker analysis of plasma ptau as a predictor of tFUS efficacy

  Baseline (pre-LIFUP)

Study Arms (4)

LIFUP Dose Group 1

ACTIVE COMPARATOR

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

Device: Low-Intensity Focused Ultrasound Pulsation (LIFUP)

LIFUP Dose Group 2

ACTIVE COMPARATOR

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

Device: Low-Intensity Focused Ultrasound Pulsation (LIFUP)

LIFUP Dose Group 3

ACTIVE COMPARATOR

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

Device: Low-Intensity Focused Ultrasound Pulsation (LIFUP)

Sham LIFUP

SHAM COMPARATOR

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.

Device: Low-Intensity Focused Ultrasound Pulsation (LIFUP)

Interventions

Low-Intensity Focused Ultrasound Pulsation (LIFUP) 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)

Also known as: transcranial focused ultrasound, tFUS, LIFUP, low intensity focused ultrasound

LIFUP Dose Group 1; LIFUP Dose Group 2; LIFUP Dose Group 3; Sham LIFUP

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Los Angeles: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

UCLA Semel Institute for Neuroscience and Behavior

Los Angeles, California, 90024, United States

RECRUITING

Related Publications (4)

• 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.

  PMID: 24060532 BACKGROUND

• 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.

  PMID: 25873429 BACKGROUND

• 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.

  PMID: 25222068 BACKGROUND

• 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.

  PMID: 21777872 BACKGROUND

Related Links

• Study Website

MeSH Terms

Conditions

Cognitive Dysfunction; Neurocognitive Disorders; Alzheimer Disease

Condition Hierarchy (Ancestors)

Cognition Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Study Officials

• Susan Y Bookheimer, PhD

  UCLA Psychiatry & Biobehavioral Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Natalie Rotstein

CONTACT

‭(310) 794-0077‬; tfus@mednet.ucla.edu

Sabrina Halavi

CONTACT

‭(310) 794-0077‬; tfus@mednet.ucla.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participants and the participants' caregivers will be blinded to arm assignment. Additionally, the person administering memory testing will be blinded to assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: June 1, 2022
• First Posted: June 14, 2022
• Study Start: September 1, 2022
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: April 16, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)