This is a prospective, non-randomized, single-arm, feasibility study to evaluate the safety and initial effectiveness of opening of the Blood-Brain Barrier with intravenous contrast agents using the ExAblate Neuro System in patients with early stage Alzheimer's Disease.
This study is a prospective, single-arm, non-randomized, feasibility, phase I trial to evaluate the safety of focal BBB opening using the ExAblate® Transcranial (220 kHz) system and Definity® ultrasound contrast in 6 patients with mild Alzheimer's Disease. This phase I trial will be divided into two stages. In the first stage, patients will undergo small volume BBB opening, 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 frontal lobe. 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 30 days. If the subject experienced BBB opening without any serious adverse effects (such as brain edema), then the subject may proceed to Stage two where a larger volume (2.5-3.0 cm) will be targeted. Subjects will be followed for an additional 60 days for safety and preliminary effectiveness.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Open BBB using ExAblate focused ultrasound and (Definity®) contrast agent
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
Change in contrast enhancement (intensity) following BBB disruption
Change in contrast enhancement (intensity) following BBB disruption to pre-sonication images as a comparative ratio measured in percent as read from MR images and normalized to the contralateral hemisphere
Time frame: Immediately post treatment
Change in amyloid uptake
Change in amyloid uptake as compared to pre treatment scans in the targeted region
Time frame: 30 days after treatments
Adverse events
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 90 days
MMSE - Mini Mental State Examination
Treatment effect on patients' dementia state
Time frame: 30 days
ADAS-Cog - Alzheimer's Disease Assessment Scale - Cognitive Behavior subscales
Treatment effect on patients' Alzheimer's disease symptoms
Time frame: 30 days
NPI - Neuropsychiatry Inventory
Treatment effect on patients' dementia
Time frame: 30 days
GDS - Geriatric Depression Scale
Treatment effect on patients' depression
Time frame: 30 days
ADCS-ADL - Alzheimer's Disease Co-operative Study - Activities of Daily Living Inventory
Treatment effect on patients' activities of daily living
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Time frame: 30 days