LIFUP for Treatment of Motor Deficits in Parkinson's Disease (LIFUP PD)

Low-Intensity Focused Ultrasound Pulsation for Treatment of Motor Deficits in Parkinson's Disease

The study will test the feasibility of using Low Intensity Focused Ultrasound Pulsation (LIFUP) to treat motor symptoms in Parkinson's Disease (PD). LIFUP is a new technique that can increase brain activity in highly specific target areas and is MRI compatible. Thus, in real-time, it is possible to directly observe how LIFUP changes the brain areas important in PD by measuring its effects on brain activity, blood flow, and brain connectivity. If successful, this research will mark the first step towards a novel, non-invasive, non-medication treatment for PD.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Device: Active LIFUP Treatment; Device: Sham LIFUP Treatment

Detailed Description

This trial is a proof-of-concept, proof-of-mechanism study of a novel neuromodulation technology - LIFUP - to treat motor symptoms in PD. Much like Deep Brain Stimulation, LIFUP can be focused on deep brain structures with high spatial accuracy, including those implicated in PD; however, it can do so non-invasively. Other non-invasive neuromodulation tools such as Transcranial Magnetic Stimulation can only target surface brain structures and are not optimal PD treatment tools. This study will test this new technology in 30 participants with PD during simultaneous resting state functional MRI, and collect pre- and post-LIFUP functional MRI, arterial spin labeling, motor performance data, and behavioral data, in a double-blind crossover trial to determine whether LIFUP: 1) will improve motor symptoms during and after treatment; 2) can modulate neural activity in the target brain region important for PD, the internal globus pallidus; and 3) enhance cortico-striatal motor circuit connectivity. All participants in this study will receive active ultrasound at one of the two in-person sessions and sham at the other.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of Parkinson's disease
2. Age 18-85
3. Fluent in the English language

Exclusion Criteria:

1. Metal implants that are not MR compatible
2. Neurological diagnosis other than Parkinson's
3. Not fluent in the English language

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, then Sham; Active Low intensity focused ultrasound pulsation (LIFUP) will be administered to the internal globus pallidus while participants are in the MRI scanner. Then, 2 weeks later, sham LIFUP will be administered.	Device: Active LIFUP Treatment; Low intensity focused ultrasound pulsation will be administered to the internal globus pallidus in 20 sonications at 650kHz, ispta.3 720mW/cm, pulse repetition frequency 100Hz, duty cycle 5%, duration 30s with 30s spacing between sonications. For active LIFUP, the device will be used with a gel pad that allows the ultrasound to pass through.; Other Names: BX Pulsar 1002; Device: Sham LIFUP Treatment; The device will be aimed at the internal globus pallidus and turned on with the same settings as the active condition; however, in this case, the device will be used with a gel pad that blocks the ultrasound from passing through, such that no ultrasound is actually being administered to the brain.
Experimental: Sham, then Active; Sham low intensity focused ultrasound pulsation (LIFUP) will be administered while participants are in the MRI scanner. Then, 2 weeks later, active LIFUP will be administered to the internal globus pallidus.	Device: Active LIFUP Treatment; Low intensity focused ultrasound pulsation will be administered to the internal globus pallidus in 20 sonications at 650kHz, ispta.3 720mW/cm, pulse repetition frequency 100Hz, duty cycle 5%, duration 30s with 30s spacing between sonications. For active LIFUP, the device will be used with a gel pad that allows the ultrasound to pass through.; Other Names: BX Pulsar 1002; Device: Sham LIFUP Treatment; The device will be aimed at the internal globus pallidus and turned on with the same settings as the active condition; however, in this case, the device will be used with a gel pad that blocks the ultrasound from passing through, such that no ultrasound is actually being administered to the brain.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor Assessment 2: 9-Hole Pegboard Dexterity Test	The participant will place and remove nine plastic pegs into a plastic pegboard. Scores are recorded as time in seconds that it takes the participant to complete the task with each hand. Analysis will compare pre- and post-treatment scores to quantify motor performance improvements.	Pre-LIFUP and Post-LIFUP at Day 1 and Day 15
Motor Assessment 1: Unified Parkinson Disease Rating Scale (UPDRS) Section 3	The participant will complete a 18-item comprehensive motor assessment that assesses elements of motor function including tremor, bradykinesia, and gait. The total score for this assessment ranges from 0 to 108 points, with higher scores indicating higher severity.	Pre-LIFUP and Post-LIFUP at Day 1 and Day 15
Motor Assessment 2: Finger Tapping (Score)	This task, which is item 3.4 on the Unified Parkinson's Disease Rating Scale (UPDRS), asks participants to tap their index finger on their thumb ten times as big and as fast as possible. Participants scores on item 3.4 with standard UPDRS scoring criteria (on a scale of 0 to 4, where a higher score indicates more severe Parkinson's symptoms i.e. worse performance) will be assessed pre and post-LIFUP. The scores reported below are for the hand on the side with worse symptoms (i.e. the side that LIFUP is intended to primarily affect).	Pre-LIFUP and Post-LIFUP at Day 1 and Day 15
Motor Assessment 2: Finger Tapping (Speed)	This task, which is item 3.4 on the Unified Parkinson's Disease Rating Scale (UPDRS), asks participants to tap their index finger on their thumb ten times as big and as fast as possible. The speed of taps will be assessed pre and post-LIFUP. Speed is calculated as [number of taps per second] times [average tap amplitude], where tap amplitude is measured on a scale of 0.0-1.0 representing the percentage of finger extension between taps, where e.g. extension to a 90 degree angle between thumb and index finger = 1.0, extension to 45 degree angle = 0.5, etc. Higher speed indicates better performance. The speed values reported below are for the hand on the side with worse symptoms (i.e. the side that LIFUP is intended to primarily affect).	Pre-LIFUP and Post-LIFUP at Day 1 and Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in BOLD fMRI Signal Between on vs. Off Blocks	BOLD data will be collected in real-time during the ultrasound sonication, which occurs in interleaved 30 second "on" and "off" blocks. Analyses will assess the statistical relationship between BOLD signal in the brain and the time series (on vs off) of the ultrasound sonication. Tabular data reported here represents the difference in BOLD activation between on and off conditions in the internal globus pallidus on the targeted side of the brain, calculated as the mean BOLD activation while LIFUP is on minus mean activation when it is off.	During LIFUP (or sham) sonication on Day 1 and Day 15
Perfusion Changes in Internal Globus Pallidus, External Globus Pallidus, and Putamen	Arterial spin labeling data will be collected before and after sonication. Analyses will assess the statistical relationship between perfusion in the targeted internal globus pallidus, external globus pallidus, and putamen pre- and post-sonication in a within-subject repeated measures design.	Pre-LIFUP and Post-LIFUP at Day 1 and Day 15

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Investigators: Principal Investigator: Susan Y Bookheimer, Ph.D., University of California, Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2022
• Primary Completion (Actual): July 24, 2024
• Study Completion (Actual): July 31, 2024

Study Registration Dates

• First Submitted: October 3, 2020
• First Submitted That Met QC Criteria: October 13, 2020
• First Posted (Actual): October 20, 2020

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Ultrasound; LIFUP
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease
• Other Study ID Numbers: IRB#20-001901

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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