Clinical trial NCT06259708: Using Low Intensity Focused Ultrasound to Modulate Deep Brain Areas for Tremor Control in Parkinson's Disease Patients.
Official title: Effectiveness of Targeting the Zona Incerta (ZI) for Tremor Control in Parkinson's Disease Patients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Parkinson Disease
Keywords: Low intensity focused ultrasound
Parkinsons disease
Tremor
Zona incerta
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Focused Ultrasound Foundation
First posted: 2024-02-14
Enrollment: 20
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The investigators will use a crossover design for this study as it requires fewer participants and removes variance between participants in the outcomes that are irrelevant to the stimulation type in comparison to other designs where each participant only receives one stimulation. All participants receive all the stimulation types (Vim-LIFU and ZI-LIFU), but the order in which they get the stimulation types is randomized.
Primary purpose: BASIC_SCIENCE

Brief summary: Researchers have found that a treatment called Magnetic Resonance guided Focused Ultrasound (MRgFUS) can effectively reduce tremors in patients with essential tremor (ET) and Parkinson's disease (PD). They noticed that ET patients initially responded better to the treatment than PD patients, but by the end of the treatment, both groups showed similar improvement. The study also suggested that targeting a specific area of the brain called the Zona Incerta (ZI) may be more beneficial for PD patients. Based on these findings, the investigators plan to use low-intensity focused ultrasound to directly modulate the ZI area and investigate the mechanisms of reduced tremors in PD patients. The investigators will also compare the effectiveness of this approach with the current target, the ventral intermediate nucleus (Vim) of the thalamus. The investigators will use a simulation model to determine the best ultrasound parameters for this new approach and will also examine the impact of the treatment on the brain's network activity using functional Magnetic Resonance Imaging. Success of this project may lay the foundation for finding a more effective target for MRgFUS treatment of PD tremor.


Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of Parkinson's disease
* Resting tremor score (MDS-UPDRS III 3.17 Rest Tremore Amplitude (RUE or LUE)) ≥ 2
* Between the ages of 40-80 years
* Hoehn and Yahr stage between 1-3 (mild to moderate PD) in the "ON" state
* Patients who are willing to have a partial (\~8 cm diameter circular area above the ear) hair shaving.

Exclusion Criteria:

* Atypical Parkinsonism
* History of essential tremor
* Dementia preventing informed consent
* Change in Parkinson's medication with the last 2 weeks
* Neurological disease other than PD, including Alzheimer's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, a brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma
* Unstable medical conditions or serious disease/conditions (e.g., cancer undergoing active treatment, poorly controlled diabetes)
* Concurrent treatment for PD with Duodopa
* Concurrent treatment for PD with deep brain stimulation (DBS)
* Thickness of the temporal bone \< 7 mm
* Individuals should also not participate if they have any of the following contraindications for undergoing fMRI scanning:
* Cardiac pacemaker, wires, or defibrillator
* Metal in eye or orbit, including the history of any eye injury involving metal fragments and increased risk due to (history of) working as a metal worker (grinding, machining, or welding)
* Ferromagnetic aneurysm clip
* Possibility of pregnancy
* Artificial heart valve
* Ear or eye implant, including cochlear implant
* Brain aneurysm clip
* Implanted drug infusion pump
* Electrical stimulator to nerves or bones
* Coil, catheter, or filter in any blood vessel
* Orthopedic hardware (artificial joint, plate, screw, rod)
* Other metallic prostheses
* Shrapnel, bullets, or other metal fragments
* Surgery, piercings or tattoos (including tattooed eyeliner) in the last six weeks
* Medication releasing skin patches (i.e. nicotine, birth control, nitroglycerine)
* History of claustrophobia

Primary outcomes:
measure: Tremor
timeFrame: At 50Hz for 40 minutes 30 minutes after intervention
measure: Tremor
timeFrame: At 50Hz for 40 minutes 30 minutes after intervention
measure: Functional connectivity
timeFrame: Once before and once immediately after intervention
Secondary outcomes:
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: University of British Columbia, DMCBH
state: British Columbia
Study officials:
affiliation: Food and Drugs Administration
name: Hongchae Baek, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Soojin Lee, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Martin J. McKeown, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: