Ultrasonic Neuromodulation for Treatment of Cognitive Impairment

Deep Brain Therapy With Low-intensity Ultrasound for Treatment of Cognitive Impairment

This study will evaluate a new form of non-invasive deep brain therapy for individuals with Alzheimer's disease. Low-intensity transcranial focused ultrasound stimulation will first be delivered using a range of stimulation parameters during psychophysical and physiological monitoring. A well-tolerated stimulation protocol will be selected for subsequent testing in a blinded randomized sham-controlled cross-over trial. The trial will evaluate brain target engagement using magnetic resonance imaging, PET imaging, and numerical scales of cognitive performance.

Study Overview

• Status: Terminated
• Conditions: Cognitive Impairment; Dementia; Alzheimer Disease
• Intervention / Treatment: Device: Diadem prototype

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Mild cognitive impairment or mild dementia due to Alzheimer's disase (AD) with confirmed AD biomarkers (Amyloid PET or CSF)
• Age 65-80
• MOCA > 18

Exclusion Criteria:

• Evidence of cerebral amyloid angiopathy or stroke within 1 year
• Clinical symptoms or findings suggestive of alternative diagnosis or co-pathology
• Inability to complete MRI
• Suicidal ideation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active stimulation; Low-intensity transcranial focused ultrasound stimulation of deep brain targets affected by Alzheimer's disease.	Device: Diadem prototype; The device delivers low-intensity ultrasonic waves into specific brain targets.
Sham Comparator: Sham stimulation; Sham stimulation that applies the device in the same way as verum but only delivers auditory sounds correspoding to the ultrasonic pulses.	Device: Diadem prototype; The device delivers low-intensity ultrasonic waves into specific brain targets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montreal Cognitive Assessment Test for Dementia (MoCA)	The MoCA is a 30-point test to detect cognitive impairment. Scores range from 0 (poor) and 30 (perfect).	Up to 3 months following study initiation
Hamilton Depression Rating Scale (HDRS-17)	This 17-item questionnaire rates the severity of depression by probing mood, feelings of guilt, suicide ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. The scores range from 0 (no symptoms) to 52 (worst possible).	Up to 3 months following study initiation
Amyloid PET	PET (positron emission tomography) combined with fluorine-18 labelled radiotracers provide brain scans that are interpreted as either amyloid-beta positive or negative.	Up to 3 months following study initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hopkins Verbal Learning Test-Revised (HVLT-R)	HVLT-R is a verbal memory test with 12 words learned over three trials, with the correct words summed for the Total Recall score (range = 0 (worst) - 36 (best)). The Delayed Recall score is the number of correct words recalled after a 20 - 25-minute delay (range = 0 (worst) - 12 (best)).	Up to 3 months following study initiation
Digit Span Memory Test	A standard test for working memory. In this test, a list of random numbers or letters is presented on a computer screen at the rate of one per second. The test begins with three numbers, increasing until the person commits errors. The average digit span for normal adults without error is seven plus or minus two. The higher the number, the more patent the working memory.	Up to 3 months following study initiation
Trail Making Test, Part A and B	The test probes visual scanning and working memory. The task is to connect a set of 25 dots as quickly as possible while maintaining accuracy. The faster the completion of Part A and Part B, the better.	Up to 3 months following study initiation

Collaborators and Investigators

• Sponsor: University of Utah

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2024
• Primary Completion (Actual): August 21, 2024
• Study Completion (Actual): August 21, 2024

Study Registration Dates

• First Submitted: November 8, 2023
• First Submitted That Met QC Criteria: November 11, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Actual): May 25, 2025
• Last Update Submitted That Met QC Criteria: May 20, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease
• Other Study ID Numbers: IRB_00173042

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No