Parkinson DiseaseNCT07695233
Pedunculopontine Nucleus Transcranial Ultrasound Stimulation as a Treatment of Freezing of Gait in Parkinson's Disease
A study testing Excitatory Stimulation and Inhibitory Stimulation in people with Parkinson Disease and Freezing of Gait Symptoms in Parkinson Disease, run by Robert Chen at 1 site in Canada.
Trial summary
This study is investigating the use of transcranial ultrasound stimulation (TUS) on the Pedunculopontine nucleus (PPN) in changing freezing of gait in people with Parkinson's disease. The PPN is noted to be involved in voluntary movements, locomotion, and muscle tone. Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Parkinson Disease, Freezing of Gait Symptoms in Parkinson Disease
- What is being tested?
- Excitatory Stimulation and Inhibitory Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteCanada
- Study dates
- 17 May 2024to Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 18-90 years of age
- Confirmed diagnosis of a movement disorder with Freezing of Gait
- Stable dopaminergic medication dose for a minimum of 4 weeks
Who cannot join
- History of stroke or seizure
- Comorbid dementia
- Scored below 22 on the Montreal Cognitive Assessment (MoCA)
- Has intracranial implant(s) or device(s)
- Has an implanted cardiac pacemaker or implantable cardioverter-defibrillator (ICD)
- Has a previous surgical intervention to treat the movement disorder such as lesioning or a DBS system in place.
Show all 12Show fewer
- Presence of metal implanted in body that is contraindicated in TMS/MRI
- Pregnancy
- Major depression/psychiatric disorder that in the opinion of the Investigator will affect patient's understanding of study procedures and willingness to abide by all procedures during the course of the study
- Is on antipsychotics, marijuana, or other recreational drugs that affect the nervous system
- Major musculoskeletal or neuromuscular disease or disorder of the hands, wrists and limbs
- Major systemic illness or infection
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
Toronto Western Hospital
Toronto, Ontario, M5T 2S8
Julian Kwok, 416-603-5800 ext. 2708, julian.kwok@uhn.ca
Robert Chen, MD
About this study
This study is investigating the use of transcranial ultrasound stimulation (TUS) on the Pedunculopontine nucleus (PPN) in changing freezing of gait in people with Parkinson's disease. The PPN is noted to be involved in voluntary movements, locomotion, and muscle tone. This will be assessed by patient-reported outcomes and analyzing the gait. The study will also investigate the effects of the stimulation on the PPN and surrounding connectivity by using magnetic resonance imaging (MRI).
Read the detailed description
To evaluate the safety, tolerability and effectiveness of Pedunculopontine nucleus transcranial ultrasound stimulation (PPN-TUS) in reducing freezing of gait (FOG) in Parkinson's disease (PD) patients using advanced gait analyses and patient-reported quality of life outcomes.
Investigate changes in brain functional connectivity caused by PPN-TUS using resting state functional magnetic (rsfMRI) and Arterial Spin Labelling (ASL).
The study will recruit 25 PD patients with FOG and 25 healthy controls, matched for age and sex, in a randomized, cross-over design.
Visit 1: Obtain anatomical MRI for TUS planning and rsfMRI for functional connectivity analysis in PD patients with FOG. This session also includes baseline clinical evaluation, kinematic gait analysis in the ON-medication state.
Between Visits 1 and 2: Structural MRI data of each participant will be processed using BabelBrain software to configure the TUS parameters. The depth required to stimulate the PPN will be calculated, and a precise model of the pressure distribution and thermal dynamics of the TUS based on individual skull thickness and geometry will be created.
Visits 2-4: The TUS will be applied using a 4-element NeuroFUS LT system (BrainBox Neuro Ltd., UK). This system allows for adjustments of the focus point of the ultrasound, which in essence changes the stimulation depth. Participants receive excitatory, inhibitory, or sham TUS for three sets of sonication, targeting the PPN bilaterally, with each stimulation set separated by one hour (accelerated TUS). We will be using excitatory and inhibitory protocols since DBS has complex excitatory and inhibitory effects and it is not known whether excitatory or inhibitory protocols will be most effective. The type of sonication (excitatory, inhibitory, or sham) will be the same within a visit but different across visits. The visits will be spaced at least a week apart to allow for a washout period. The stimulation will target both left and right PPN, sonicating each side sequentially with a 1-minute break in between to allow adjustment of the transducer. The order of which side is to be stimulated first will be counterbalanced across participants. Both hemispheres will be stimulated with the same condition (e.g., both sham if it is a sham session). Functional connectivity using rsfMRI and clinical assessments will be measured pre- and post-sonication.
Healthy subjects will undergo MRI study in one session to establish the normal range for rsfMRI and CBF measured by ASL. This will allow us to establish whether the rsfMRI and CBF findings in PD patients at baseline are normal and whether TUS of PPN normalize these patterns.
- Being tested
- Excitatory Stimulation, Inhibitory Stimulation, Sham
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Excitatory StimulationDevice
Excitatory Stimulation to the PPN
Inhibitory StimulationDevice
Inhibitory Stimulation to the PPN
ShamDevice
Sham stimulation to PPN
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Active comparator | All participants will receive excitatory, inhibitory, and sham stimulation to the PPN. The order that they receive it is randomized across Visits 2 - 4. All stimulation within a visit will be the same. Receives: Device: Excitatory Stimulation; Device: Inhibitory Stimulation; Device: Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
New Freezing of Gait Questionnaire
Measured: Occurs twice at Visits 2, 3, and 4. For each of those visits, it will be conducted once before stimulation and another after stimulation.
Timed Up-and-Go Task
Measured: Occurs twice at Visits 2, 3, and 4. For each of those visits, it will be conducted once before stimulation and another after stimulation.
ZenoTM Walkway
Mat that detects pressure data during standing and walking to evaluate gait such as speed, profile, step time, step length, strid time, stride length, and more.
Measured: Occurs twice at Visits 2, 3, and 4. For each of those visits, it will be conducted once before stimulation and another after stimulation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2026
- Study start17 May 2024
- Primary completionDec 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Robert Chen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Robert Chen, University Health Network, Toronto
- Investigators
- Robert Chen, MD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07695233
- Sponsor's protocol ID
- 20-5740 #8
- Status last verified
- Feb 2026
- First submitted
- 22 Feb 2026
- Last updated
- 10 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pedunculopontine Nucleus Transcranial Ultrasound Stimulation as a Treatment of Freezing of Gait in Parkinson's Disease
- ClinicalTrials.gov ID
- NCT07695233
- Acronym / sponsor ID
- 20-5740 #8
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Robert ChenUniversity, hospital or other
- Study start
- 17 May 2024 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 10 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is investigating the use of transcranial ultrasound stimulation (TUS) on the Pedunculopontine nucleus (PPN) in changing freezing of gait in people with Parkinson's disease. The PPN is noted to be involved in voluntary movements, locomotion, and muscle tone. This will be assessed by patient-reported outcomes and analyzing the gait. The study will also investigate the effects of the stimulation on the PPN and surrounding connectivity by using magnetic resonance imaging (MRI).
Detailed description
To evaluate the safety, tolerability and effectiveness of Pedunculopontine nucleus transcranial ultrasound stimulation (PPN-TUS) in reducing freezing of gait (FOG) in Parkinson's disease (PD) patients using advanced gait analyses and patient-reported quality of life outcomes.
Investigate changes in brain functional connectivity caused by PPN-TUS using resting state functional magnetic (rsfMRI) and Arterial Spin Labelling (ASL).
The study will recruit 25 PD patients with FOG and 25 healthy controls, matched for age and sex, in a randomized, cross-over design.
Visit 1: Obtain anatomical MRI for TUS planning and rsfMRI for functional connectivity analysis in PD patients with FOG. This session also includes baseline clinical evaluation, kinematic gait analysis in the ON-medication state.
Between Visits 1 and 2: Structural MRI data of each participant will be processed using BabelBrain software to configure the TUS parameters. The depth required to stimulate the PPN will be calculated, and a precise model of the pressure distribution and thermal dynamics of the TUS based on individual skull thickness and geometry will be created.
Visits 2-4: The TUS will be applied using a 4-element NeuroFUS LT system (BrainBox Neuro Ltd., UK). This system allows for adjustments of the focus point of the ultrasound, which in essence changes the stimulation depth. Participants receive excitatory, inhibitory, or sham TUS for three sets of sonication, targeting the PPN bilaterally, with each stimulation set separated by one hour (accelerated TUS). We will be using excitatory and inhibitory protocols since DBS has complex excitatory and inhibitory effects and it is not known whether excitatory or inhibitory protocols will be most effective. The type of sonication (excitatory, inhibitory, or sham) will be the same within a visit but different across visits. The visits will be spaced at least a week apart to allow for a washout period. The stimulation will target both left and right PPN, sonicating each side sequentially with a 1-minute break in between to allow adjustment of the transducer. The order of which side is to be stimulated first will be counterbalanced across participants. Both hemispheres will be stimulated with the same condition (e.g., both sham if it is a sham session). Functional connectivity using rsfMRI and clinical assessments will be measured pre- and post-sonication.
Healthy subjects will undergo MRI study in one session to establish the normal range for rsfMRI and CBF measured by ASL. This will allow us to establish whether the rsfMRI and CBF findings in PD patients at baseline are normal and whether TUS of PPN normalize these patterns.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Active comparator | Device: Excitatory Stimulation, Device: Inhibitory Stimulation, Device: ShamAll participants will receive excitatory, inhibitory, and sham stimulation to the PPN. The order that they receive it is randomized across Visits 2 - 4. All stimulation within a visit will be the same. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 18-90 years of age
- Confirmed diagnosis of a movement disorder with Freezing of Gait
- Stable dopaminergic medication dose for a minimum of 4 weeks
Key exclusion criteria (12 listed)
- History of stroke or seizure
- Comorbid dementia
- Scored below 22 on the Montreal Cognitive Assessment (MoCA)
- Has intracranial implant(s) or device(s)
- Has an implanted cardiac pacemaker or implantable cardioverter-defibrillator (ICD)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Excitatory StimulationExcitatory Stimulation to the PPN | Device | Arm 1 |
| Inhibitory StimulationInhibitory Stimulation to the PPN | Device | Arm 1 |
| ShamSham stimulation to PPN | Device | Arm 1 |
Primary outcome
New Freezing of Gait Questionnaire
Time frame: Occurs twice at Visits 2, 3, and 4. For each of those visits, it will be conducted once before stimulation and another after stimulation.
Timed Up-and-Go Task
Time frame: Occurs twice at Visits 2, 3, and 4. For each of those visits, it will be conducted once before stimulation and another after stimulation.
ZenoTM Walkway
Time frame: Occurs twice at Visits 2, 3, and 4. For each of those visits, it will be conducted once before stimulation and another after stimulation.
Mat that detects pressure data during standing and walking to evaluate gait such as speed, profile, step time, step length, strid time, stride length, and more.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Robert Chen, MD principal investigator
University Health Network, Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Excitatory Stimulation and Inhibitory Stimulation in people with Parkinson Disease and Freezing of Gait Symptoms in Parkinson Disease, run by Robert Chen at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Julian Kwok (416-603-5800 ext. 2708, julian.kwok@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
New Freezing of Gait Questionnaire (time frame: Occurs twice at Visits 2, 3, and 4. For each of those visits, it will be conducted once before stimulation and another after stimulation.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2026.