Optimizing Parameters of Low-Intensity Focused Ultrasound for Cortical Modulation in Stroke Patients (LIFU)

The purpose of this research study is to find out the optimal intensity and frequency of Low Intensity Focused Ultrasound (LIFU) that is safe and tolerable in people who have had a stroke.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Device: Low Intensity Focused Ultrasonic Stimulation; Device: Low Intensity Focused Ultrasonic Stimulation Frequency

Detailed Description

Aim 1 is to determine the optimal intensity of Low Intensity Focused Ultrasound stimulation (LIFUS) in stroke patients in terms of safety. We will investigate the optimal spatial-peak temporal-average intensity/ISPTA in the range of 0(or sham) W/cm2 to 8 W/cm2. Safety will be investigated by assessing clinically detectable signs and symptoms by monitoring vital signs and surveying subjects with a questionnaire before and after each stimulation session, and additionally by detecting subclinical neuronal injury using MRI/DWI. Aim 1 requires up to 36 subjects.

Aim 2 is to determine the optimal frequency of LIFU stimulation in stroke patients in terms of cortical excitability. Stroke subjects undergo each of the 5 frequency levels (0.35 MHz; 0.5 MHz; 0.75 MHz, 1.0 MHz and 1.5 MHz) on 5 different days with at least one day washout. The intensity (ISPTA) will set up at the level that is determined from Aim 1. Cortical excitability is measured by the amplitude of motor evoked potentials (MEPs) induced by Transcranial Magnetic Stimulation (TMS) from the Abductor Pollicis Brevis (ABP) muscle of the affected side. MEPs will be recorded pre- and post-stimulation to determine the optimal intensity for maximal cortical excitability from the hemisphere where the lesion is located. Aim 2 requires 18 subjects.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ≥ 21 years old of any gender and race;
2. Clinical ischemic stroke or hemorrhagic (confirmed by CT or MRI) that occurred >= 2 months ago
3. Predominantly unilateral motor impairment with FM-UE score ≤ 62/66;
4. MEPs are inducible from a hand muscle on the affected side (i.e. Abductor Pollicis Brevis (APB) muscle).

Exclusion Criteria:

1. Any concomitant neurological disorder affecting arm function;
2. Documented history of severe dementia with or without medication before stroke;
3. Subject is unable to do the motor learning practice at the baseline;
4. Presence of any MRI/TMS/ultrasonic stimulation risk factors: an electrically, magnetically, or mechanically activated metal or nonmetal implant including cardiac pacemaker, intracerebral vascular clips, or any other electrically sensitive support system; non-fixed metal in any part of the body; pregnancy (the effect of TMS/ultrasonic stimulation on the fetus is unknown); no history of seizure before or after the stroke; preexisting scalp lesion or wound or bone defect or hemicraniectomy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Low Intensity Focused Ultrasonic Stimulation; There are different combinations of intensity and frequency with LIFUS

Device: Low Intensity Focused Ultrasonic Stimulation; Brain stimulation using ultrasonic stimulation in a sequence of increasing intensity (sham, 1 W/CM2, 2 W/CM2, 4 W/CM2, 6 W/CM2, 8 W/CM2); Device: Low Intensity Focused Ultrasonic Stimulation Frequency; Brain stimulation using ultrasonic stimulation of intensity level determined from intervention 1 at progressively increasing frequency levels (0.35 MHz; 0.5 MHz; 0.75 MHz, 1.0 MHz and 1.5 MHz)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Outcomes, as measured by the number of participants with a "major response" - Aim 1 of study	Safety outcomes are measured by "major response" which is pre-defined by any of the following event; Second degree skin injury;; Clinical seizure;; New lesion on DWI sequence of MRI scan and the lesion not explained by any other cause(s) or decreased ADC under the transducer stimulating motor cortex area;; Patient discontinues from the study due to any reason This is a 3+3 study design. Basically, 3 subjects are recruited at a given intensity level. If major response occurs in ≥2/3 study subjects then the trial will stop at this intensity level. If ≤ 3 subjects shows major response, 3 more subjects are recruited to further test safety at the same intensity level; if no major response occurs (i.e. major response ≤ 1/6), the intensity will be escalated to next higher level; if major response occurs ≥ 2/6 subjects, then the trial will terminate at this intensity level. The sequence for intensity escalation is sham > 1 W/cm2 > 2 W/cm2 > 4W/cm2 > 6W/cm2 > 8W/cm2.	At any point during or immediately following intervention on day of LIFUS application
Cortical Excitability - Aim 2 of the study	Cortical excitability is measured by Motor evoked potential(MEP) amplitude using Transcranial Magnetic Stimulation. Mean changes on MEP ( Pre- Post- Ultrasonic Stimulation on the same day) is compared across 5 different stimulation frequency groups.	Immediately after ultrasonic stimulation

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Wayne Feng, Duke Health

Publications and helpful links

General Publications

• Huang Z, Charalambous CC, Chen M, Kim T, Sokhadze E, Song A, Jung SH, Shekhar S, Feld JA, Jiang X, Feng W. Low intensity focused ultrasound stimulation in stroke: A phase I safety & feasibility trial. Brain Stimul. 2025 Jan 20;18(1):179-187. doi: 10.1016/j.brs.2025.01.015. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2021
• Primary Completion (Actual): April 17, 2024
• Study Completion (Actual): April 17, 2024

Study Registration Dates

• First Submitted: August 16, 2021
• First Submitted That Met QC Criteria: August 16, 2021
• First Posted (Actual): August 23, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 25, 2025
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: stroke; brain stimulation; low intensity focused ultrasound; ultrasonic stimulation
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: Pro00106556

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: we will follow the American Heart Association/American Stroke Association data sharing policy per grant requirement

Drug and device information, study documents

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