A Study to Evaluate Temporary Blood Brain Barrier Disruption in Patients With Parkinson's Disease Dementia

NCT ID: NCT03608553

Last Updated: 2025-12-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-26
• Study Completion Date: 2022-08-09

Brief Summary

The goal of this prospective, non-randomized, single-arm, feasibility study is to develop data to evaluate the safety and initial efficacy of this treatment (temporary disruption of the BBB) using this ExAblate Model 4000 Type 2 System in patients with mild to moderate Parkinson´s Disease Dementia

Detailed Description

This study is a prospective, single-arm, non-randomized, safety and feasibility trial of focal BBB disruption using the ExAblate® Model 4000 Type 2 (220 kHz) system with Luminity® ultrasound contrast in 10 patients with mild to moderate Parkinson's Disease Dementia. Patients, together with their caregivers, will be approached after their identification by a team of neurosurgeons and neurologists who specialize in the management of cognitive disorders and functional neurosurgery. The study will be discussed with them, and all patients, or their legal representatives will provide informed consent to participate in the study.

This first in human trial will be divided into two stages. In the first stage, patients will undergo small volume BBB disruption, establishing the minimum required sonication parameters to open the BBB, as evidenced by gadolinium enhancement on T1-weighted MRI. Stage I is defined as a discrete region of approximately 9 mm x 9 mm area in the right parietooccipitotemporal cortex. Multiple sonications will be performed starting at low energy and ramping up until the BBB is observed to open.

The subjects will then be removed from the ExAblate® Neuro device and followed for safety for 2 weeks. If the subject experienced BBB disruption without any serious adverse effects (such as brain edema), then the subject may proceed to Stage II where a larger volume (2.5-3.0 cm) will be targeted. Subjects will be followed for an additional 2 weeks for safety and preliminary effectiveness.

The staged approach will allow determination of:

1. Safety of BBB disruption

2. Feasibility of disruption the BBB

3. Reversibility of BBB disruption

4. Reproducibility of BBB disruption

Conditions

Parkinsons Disease With Dementia

Keywords

MRgFUS; BBB; Blood Brain Barrier Disruption

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ExAblate

ExAblate MR Guided Focused Ultrasound

Group Type: EXPERIMENTAL

MR Guided Focused Ultrasound

Intervention Type: DEVICE

Blood Brain Barrier Disruption using FUS

Interventions

MR Guided Focused Ultrasound

Blood Brain Barrier Disruption using FUS

Intervention Type: DEVICE

Other Intervention Names

ExAblate

Eligibility Criteria

Inclusion Criteria

1. Parkinson´s Disease, according to the UK Parkinson´s Disease Society Brain Bank (Gelb et al. 1999)

2. Parkinson´s Disease patients diagnosed with mild-moderate dementia according to the Movement Disorders Criteria (Emre et al. 2007)

3. Able and willing to give informed consent, or has delegated this to a substitute decision maker.

4. Mini Mental State Exam (MMSE) scores ≥16 (able to complete a Neuropsychological evaluation)

5. Geriatric Depression Scale (GDS) score of ≤ 20

6. Age: 60-80 years

7. Able to attend all study visits (i.e., life expectancy of 1 year).

Exclusion Criteria

1. Clips or other metallic implanted objects in the skull or the brain, except shunts

2. Significant cardiac disease or unstable hemodynamic status

3. Uncontrolled hypertension (systolic > 150 and diastolic BP > 100 on medication)

4. Medications known to increase risk of hemorrhage, (e.g.: patients should be off of ASA for at least 7 days prior to treatment) or anticoagulants

5. History of a bleeding disorder

6. Significant depression and at potential risk of suicide

7. Known sensitivity/allergy to gadolinium

8. Any contraindications to MRI scanning

9. History of seizure disorder or epilepsy

10. History of drug or alcohol use disorder who may be at higher risk for seizure, infection, or poor executive functioning

11. Chronic breathing disorders

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

InSightec

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jose Obeso, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Director of CINAC

Locations

HM Hospitales Puerta del Sur - CINAC

Móstoles, Madrid, Spain

Countries

Spain

References

Pineda-Pardo JA, Gasca-Salas C, Fernandez-Rodriguez B, Rodriguez-Rojas R, Del Alamo M, Obeso I, Hernandez-Fernandez F, Trompeta C, Martinez-Fernandez R, Matarazzo M, Mata-Marin D, Guida P, Duque A, Albillo D, Plaza de Las Heras I, Montero JI, Foffani G, Toltsis G, Rachmilevitch I, Blesa J, Obeso JA. Striatal Blood-Brain Barrier Opening in Parkinson's Disease Dementia: A Pilot Exploratory Study. Mov Disord. 2022 Oct;37(10):2057-2065. doi: 10.1002/mds.29134. Epub 2022 Jun 28.

Reference Type: DERIVED

PMID: 35765711 (View on PubMed)

Gasca-Salas C, Fernandez-Rodriguez B, Pineda-Pardo JA, Rodriguez-Rojas R, Obeso I, Hernandez-Fernandez F, Del Alamo M, Mata D, Guida P, Ordas-Bandera C, Montero-Roblas JI, Martinez-Fernandez R, Foffani G, Rachmilevitch I, Obeso JA. Blood-brain barrier opening with focused ultrasound in Parkinson's disease dementia. Nat Commun. 2021 Feb 3;12(1):779. doi: 10.1038/s41467-021-21022-9.

Reference Type: DERIVED

PMID: 33536430 (View on PubMed)

Other Identifiers

PD008

Identifier Type: -

Identifier Source: org_study_id