Unilateral and Staged Bilateral Pallidothalamic Tractotomy Using Exablate MRgFUS in Advanced Parkinson's Disease.

NCT07764874 | Not Yet Recruiting FDA Device

• 1 other identifier: PD018
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a randomized clinical trial evaluating a focused ultrasound treatment for people with advanced Parkinson's disease (PD) who have disabling motor complications and symptoms. The study uses the Exablate Neuro System, which delivers MR-guided Focused Ultrasound (MRgFUS). This technology focuses ultrasound energy on a specific brain target and generates heat to create a small lesion (ablation) without making a surgical incision. The target in this study is the Pallidothalamic Tract (PTT), a pathway involved in the abnormal brain circuits that contribute to Parkinson's symptoms and complications. This study is evaluating whether treating one side of the brain or treating both sides (in separate procedures) provides better outcomes for people with advanced Parkinson's disease who have motor complications and symptoms. The main outcome measure is the change in the MDS-UPDRS Part III Upper/Lower Extremity (ULE) score at 3 months after first and second side treatment, compared with the respective control groups. MDS-UPDRS Part III is a standard clinical scale used to assess Parkinson's motor symptoms. ULE score focuses on motor function in the arms and legs. Assessments are performed in the OFF-medication state, meaning Parkinson's medications are temporarily withheld so that the treatment effect can be measured more accurately. In addition improvement in motor complications will be assessed with MDS-UPDRS Part IV and Patient diaries.

Conditions

Parkinson Disease

Keywords

Exablate; MRgFUS; Pallidothalamic Tract

Outcome Measures

Primary Outcomes (2)

• MDS-UPRDS Part III ULE score in the OFF-medication (unilateral treatment)

  Between-group difference (Active Group 1 vs. Control Group 1) in the treatment effect (point change) in the MDS-UPRDS Part III ULE score in the OFF-medication state from Baseline to 3 month. This assessment will be performed by a Movement Disorders neurologist blinded to patient study group allocation.

  3 Months

• MDS-UPRDS Part III ULE score in the OFF-medication (bilateral treatment)

  Between-group difference (Active Group 2 vs. Control Group 2) in the treatment effect (point change) in the MDS-UPRDS Part III ULE score in the OFF-medication state from Baseline to 3 month. This assessment will be performed by a Movement Disorders neurologist blinded to patient study group allocation.

  3 Months

Secondary Outcomes (9)

• MDS-UPDRS III Total score in the OFF-medication state

  1 Month, 3 Months, 6 Months, 12 Months

• MDS-UPDRS Part III OFF ULE score

  1 Month, 3 Months, 6 Months, 12 Months

• MDS-UPDRS Part III ON Total score

  1 Month, 3 Months, 6 Months, 12 Months

• MDS-UPDRS Part IV Total score

  1 Month, 3 Months, 6 Months, 12 Months

• Number of hours per day in ON time without troublesome dyskinesia- as measured by patient diaries (unilateral)

  1 Month, 3 Months, 6 Months, 12 Months

Study Arms (5)

Active Group 1_Unilateral Exablate Pallidothalamic Tractotomy

EXPERIMENTAL

Subjects will undergo the 1st side Exablate procedure (\< 30 days after randomization) and will be followed for 6 months. At their Month 6 visit, subjects will have their re-baseline assessment and undergo staged randomization for the 2nd side treatment.

Device: Unilateral Exablate MRgFUS Pallidothalamic Tractotomy

Control Group 1_Best Medical Treatment (BMT)

ACTIVE COMPARATOR

Subjects will have their standard of care (SOC) treatment adjusted to best effect (BMT), and will be followed for 3 months. After their Month 3 visit, subjects will cross over to receive the 1st side treatment and be followed for 6 months. At their Month 6 visit, subjects will have their Treatment 2 re-baseline assessment and undergo staged randomization for the 2nd side treatment.

Drug: Best Medical Treatment (BMT)

Active Group 2_Staged Bilateral Exablate Pallidothalamic Tractotomy

EXPERIMENTAL

Subjects will undergo the 2nd side Exablate procedure (\< 30 days after re-baseline assessment, and will be followed for 12 months.

Device: Unilateral Exablate MRgFUS Pallidothalamic Tractotomy; Device: Staged Bilateral Exablate Pallidothalamic Tractotomy

Control Group 2_BMT after Unilateral Exablate Pallidothalamic Tractotomy

ACTIVE COMPARATOR

Subjects will continue with their SOC BMT and will be followed for 3 months. After their Month 3 visit, subjects will cross over to receive the 2nd side treatment and be followed for 12 months.

Device: Unilateral Exablate MRgFUS Pallidothalamic Tractotomy; Drug: Best Medical Treatment (BMT)

Reference Group_BMT with low SDR

ACTIVE COMPARATOR

Subjects will be offered the option to receive best medical treatment and will be followed to capture natural disease progression at approximately the same time schedule as patients in the randomized groups (\~ every 3 - 6 months for up to 24 months).

Drug: Best Medical Treatment (BMT)

Interventions

Unilateral Exablate MRgFUS Pallidothalamic Tractotomy DEVICE

1st side Exablate MRgFUS Pallidothalamic Tractotomy for Parkinson's Disease

Active Group 1_Unilateral Exablate Pallidothalamic Tractotomy; Active Group 2_Staged Bilateral Exablate Pallidothalamic Tractotomy; Control Group 2_BMT after Unilateral Exablate Pallidothalamic Tractotomy

Staged Bilateral Exablate Pallidothalamic Tractotomy DEVICE

2nd side staged Exablate MRgFUS Pallidothalamic Tractotomy for Parkinson's Disease

Active Group 2_Staged Bilateral Exablate Pallidothalamic Tractotomy

Best Medical Treatment (BMT) DRUG

Subjects will be managed according to conventional therapeutic guidelines (i.e., best medical treatment) for Parkinson's Disease

Control Group 1_Best Medical Treatment (BMT); Control Group 2_BMT after Unilateral Exablate Pallidothalamic Tractotomy; Reference Group_BMT with low SDR

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women, age 30 years and older
• Subject is able and willing to give informed consent and able to attend all study visits
• Subject with a diagnosis of idiopathic PD by UK Brain Bank Criteria as confirmed by a movement disorder neurologist at the site.
• Subject is interested in receiving bilateral treatment if they qualify.
• Subject is Levodopa responsive as defined by at least a 30% reduction in MDS-UPDRS motor subscale in the ON vs OFF medication state.
• Subject has MDS-UPDRS Part III OFF ULE score of ≥ 15 on each side in the meds OFF condition.
• Subject experiencing motor complications of PD on optimum medical treatment characterized by dyskinesia (MDS-UPDRS item 4.2 score of ≥ 2) OR Motor fluctuations (MDS-UPDRS item 4.4 score of ≥ 2)
• Subject is on a stable dose of all PD medications for 30 days prior to screening visit PD assessments as determined by medical records
• Subject is able to communicate sensations during the Exablate procedure.
• Subject's pallidothalamic region can be targeted by the Exablate device.

You may not qualify if:

• Subject with severe premorbid risks as specified in the MDS-UPDRS Part II subsection motor aspects of experiences of daily living scores:
• or 4 on question 2.1 (speech) OR
• or 4 on question 2.3 (chewing and swallowing) OR
• on question 2.2 (saliva and drooling).
• Subject where there is suspicion that Parkinsonian symptoms are a side effect from neuroleptic medications.
• Subject has an MMSE score \< 24.
• Subject has other central neurodegenerative disease suspected on neurological examination. These include: multisystem atrophy, progressive supranuclear palsy, corticobasal syndrome, dementia with Lewy bodies, and Alzheimer's disease.
• Subject with unstable psychiatric disease, uncontrolled depressive symptoms, psychosis, delusions, hallucinations, or suicidal ideation.
• Female subject who is pregnant.
• Female subject of childbearing potential not willing to use contraceptives throughout the duration of the study (\~ 24 months)
• Subject exhibiting any behavior(s) consistent with ethanol or substance abuse.
• Subject with unstable cardiac status or severe hypertension.
• Subject with history of abnormal bleeding, hemorrhage, or coagulopathy.
• Subject with cerebrovascular disease.
• Subject is receiving anticoagulant (e.g., warfarin) or antiplatelet (e.g., aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage (e.g., Avastin) within one month of focused ultrasound procedure.

Sponsors & Collaborators

• InSightec: lead

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Joohi Jimenez-shahed, MD

  Mount Sinai, Clinical Neurosciences Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elisa Cerutti, PhD

CONTACT

+39 3459182413; elisac@insightec.com

Jai Shetake, PhD

CONTACT

+1 469 426 1022; jais@insightec.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The study will be assessor-blinded at the site level. During all follow-up clinical assessments, all study subjects will be asked to wear a head cover to hide whether they underwent the required pre-treatment head-shaving (active group) or not (control group).
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a 2-stage randomized controlled trial. Stage 1: Subjects will be randomized (2:1) for treatment on one side of the brain vs. BMT for 3 months before being allowed to receive treatment on the 1st side (if eligible). Stage 2: After 6 months post-1st side treatment (and confirmation that they are still eligible to receive their 2nd side treatment), patients will be randomized (2:1) again for treatment on the 2nd side of the brain vs. BMT for 3 months before being allowed to receive treatment on the 2nd side (if eligible). Patients fulfilling all inclusion/exclusion criteria except for the SDR (skull density ratio) requirements (and so anatomically not able to undergo MRgFUS) will be offered the option to receive best medical treatment and will be formally followed as a reference comparator for up to 2 years.

Study Record Dates

• First Submitted: August 10, 2026
• First Posted: August 14, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): June 1, 2031
• Last Updated: August 14, 2026

Record last verified: 2026-08