Parkinson Disease
Conditions
Keywords
LIFUP, Ultrasound
Brief summary
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.
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.
Interventions
DEVICEActive 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.
DEVICESham 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.
Sponsors
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
All participants complete two identical in-person testing and LIFUP sessions. At one session, the device will be used with a gel pad that allows ultrasound to pass through, and at the other session, it will be used with a gel pad that blocks the ultrasound. The order of conditions is randomized and counterbalanced across participants. The two gel pads look identical beyond a label differentiating them, and neither the participants nor the person administering ultrasound will know whether sham or active is being administered at a given session.
Intervention model description
Participants will be assigned to both study arms; the order in which they complete the arms will be randomized and counterbalanced. The two visits will be spaced apart by 2 weeks.
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Motor Assessment 1: Unified Parkinson Disease Rating Scale (UPDRS) Section 3 | Pre-LIFUP and Post-LIFUP at Day 1 and Day 15 | 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. |
| Motor Assessment 2: Finger Tapping (Score) | Pre-LIFUP and Post-LIFUP at Day 1 and Day 15 | 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). |
| Motor Assessment 2: Finger Tapping (Speed) | Pre-LIFUP and Post-LIFUP at Day 1 and Day 15 | 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). |
| Motor Assessment 2: 9-Hole Pegboard Dexterity Test | Pre-LIFUP and Post-LIFUP at Day 1 and Day 15 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in BOLD fMRI Signal Between on vs. Off Blocks | During LIFUP (or sham) sonication on Day 1 and Day 15 | 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. |
| Perfusion Changes in Internal Globus Pallidus, External Globus Pallidus, and Putamen | Pre-LIFUP and Post-LIFUP at Day 1 and Day 15 | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSusan Y Bookheimer, Ph.D.
University of California, Los Angeles
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 65.3 years STANDARD_DEVIATION 9.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 29 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 31 |
| other Total, other adverse events | 5 / 30 | 6 / 31 |
| serious Total, serious adverse events | 0 / 30 | 0 / 31 |
Outcome results
None listed