Blood-Brain-Barrier Opening Using Focused Ultrasound With IV Contrast Agents in Patients With Early Alzheimer's Disease (BBB-Alzheimers)
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ClinicalTrials.gov Identifier: NCT02986932 |
Recruitment Status :
Completed
First Posted : December 8, 2016
Last Update Posted : June 14, 2018
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Condition or disease | Intervention/treatment | Phase |
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Alzheimer Disease | Device: BBB opening | Not Applicable |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 6 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | Transcranial ExAblate |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Study Start Date : | December 2016 |
Actual Primary Completion Date : | December 2017 |
Actual Study Completion Date : | December 2017 |

Arm | Intervention/treatment |
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Experimental: BBB opening
ExAblate focused ultrasound under MRI-guidance delivered through the intact human skull in conjunction with timed intravenous ultrasound contrast agents (Definity®) to temporarily and focally open the BBB.
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Device: BBB opening
Open BBB using ExAblate focused ultrasound and (Definity®) contrast agent |
- 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
- Change in amyloid uptake [ Time Frame: 30 days after treatments ]Change in amyloid uptake as compared to pre treatment scans in the targeted region
- Adverse events [ Time Frame: 90 days ]Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
- MMSE - Mini Mental State Examination [ Time Frame: 30 days ]Treatment effect on patients' dementia state
- ADAS-Cog - Alzheimer's Disease Assessment Scale - Cognitive Behavior subscales [ Time Frame: 30 days ]Treatment effect on patients' Alzheimer's disease symptoms
- NPI - Neuropsychiatry Inventory [ Time Frame: 30 days ]Treatment effect on patients' dementia
- GDS - Geriatric Depression Scale [ Time Frame: 30 days ]Treatment effect on patients' depression
- ADCS-ADL - Alzheimer's Disease Co-operative Study - Activities of Daily Living Inventory [ Time Frame: 30 days ]Treatment effect on patients' activities of daily living

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Ages Eligible for Study: | 55 Years to 85 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Probable AD consistent with NIA/AA criteria (McKhann, Alzheimer & Dementia 2011)
- Modified Hachinski Ischemia Scale (MHIS) score of <= 4.
- 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:
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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
- History of a bleeding disorder, coagulopathy or a history of spontaneous hemorrhage or use of anticoagulants
- Abnormal coagulation profile (PLT < 100,00/μl), PT (>14 sec) or PTT (>36 sec), and INR > 1.3
- No more than 1 non-strategic lacune <1.5 cm
- Known cerebral or systemic vasculopathy
- Significant depression and at potential risk of suicide
- Known sensitivity/allergy to gadolinium (an alternative product may be used), Definity or any of its components.
- Any contraindications to MRI scanning such as metallic implants, claustrophibia or too large for MRI scanner
- Untreated, uncontrolled sleep apnea
- Impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2
- Does not have a reliable caregiver in frequent contact with the patient and can accompany the patient to the clinic and treatment or be available by telephone at designated times. Participants living in retirement homes may be included. Caregiver not willing to sign the Informed Consent Form
- Respiratory: chronic pulmonary disorders e.g. severe emphysema, pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area, patients with a history of drug allergies, asthma or hay fever, and multiple allergies where the benefit/risk of administering Definity® is considered unfavorable by the study physicians in relation to the product monograph for Definity.
- Currently in a clinical teial involving investigational product.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02986932
Canada, Ontario | |
Sunnybrook Health Sciences Centre | |
Toronto, Ontario, Canada, M4N 3M5 |
Principal Investigator: | Nir Lipsman, MD, PhD | Sunnybrook Health Sciences Centre |
Responsible Party: | InSightec |
ClinicalTrials.gov Identifier: | NCT02986932 |
Other Study ID Numbers: |
AL001 |
First Posted: | December 8, 2016 Key Record Dates |
Last Update Posted: | June 14, 2018 |
Last Verified: | June 2018 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Blood-Brain Barrier |
Alzheimer Disease Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases |
Tauopathies Neurodegenerative Diseases Neurocognitive Disorders Mental Disorders |