A Study to Evaluate the Safety and Feasibility of Blood-Brain Barrier (BBB) Opening Using Transcranial MR-Guided Focused Ultrasound With Intravenous Ultrasound Contrast Agents in Patients With Early Alzheimer's Disease
Overview
- Phase
- N/A
- Intervention
- Not specified
- Conditions
- Alzheimer Disease
- Sponsor
- InSightec
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Change in contrast enhancement (intensity) following BBB disruption
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Probable AD consistent with NIA/AA criteria (McKhann, Alzheimer \& Dementia 2011)
- •Modified Hachinski Ischemia Scale (MHIS) score of \<=
- •Mini Mental State Exam (MMSE) scores 18-28
- •Short form Geriatric Depression Scale (GDS) score of \<= 6
- •Has a Florbetaben PET scan consistent with the presence of amyloid pathology in the proposed target region (right frontal lobe)
- •Able to communicate sensations during the ExAblate® MRgFUS procedure.
Exclusion Criteria
- •MRI findings:
- •Active infection/inflammation
- •Acute or chronic hemorrhages, specifically \> 4 lobar microbleeds, and no siderosis or macrohemorrhages
- •Tumor/space occupying lesion
- •Meningeal enhancement
- •More than 30% of the skull area traversed by the sonication pathway is covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp
- •Clips or other metallic implanted objects in the skull or the brain, except shunts; other metallic objects implanted in body
- •Significant cardiac disease or unstable hemodynamic status including:
- •Uncontrolled hypertension on medication or abnormal ECG
- •Medications known to increase risk of hemorrhage, (e.g.: patients should be off of aspirin or another anticoagulants for at least 7 days prior to treatment) or anticoagulants (class I and III) or off Avastin for 30 days
Outcomes
Primary Outcomes
Change in contrast enhancement (intensity) following BBB disruption
Time Frame: Immediately post treatment
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
Secondary Outcomes
- MMSE - Mini Mental State Examination(30 days)
- ADAS-Cog - Alzheimer's Disease Assessment Scale - Cognitive Behavior subscales(30 days)
- Change in amyloid uptake(30 days after treatments)
- Adverse events(90 days)
- NPI - Neuropsychiatry Inventory(30 days)
- GDS - Geriatric Depression Scale(30 days)
- ADCS-ADL - Alzheimer's Disease Co-operative Study - Activities of Daily Living Inventory(30 days)