Clinical trial NCT03671889: ExAblate Blood-Brain Barrier (BBB) Disruption for the Treatment of Alzheimer's Disease
Official title: Assessment of Safety and Efficacy of ExAblate Blood-Brain Barrier Disruption for the Treatment of Patients With Probable Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Alzheimer Disease
Keywords: Alzheimer Disease
Alzheimer Syndrome
Magnetic Resonance guided Focal Ultrasound (MRgFUS)
Blood-Brain Barrier
ExAblate
Lead sponsor: InSightec
Sponsor class: INDUSTRY
First posted: 2018-09-14
Enrollment: 150
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Subjects who meet study eligibility will undergo treatment procedures
Primary purpose: DEVICE_FEASIBILITY

Brief summary: The purpose of this study is to evaluate the safety and efficacy of the ExAblate Model 4000 Type 2.0 System as a tool to disrupt the blood-brain barrier (BBB) in patients with probable Alzheimer's Disease (AD).

Detailed description: This is a prospective, multi-center, single-arm study to evaluate the safety and efficacy of BBB disruption using the ExAblate Model 4000 Type 2.0 (220 kHz) system. Patients with diagnosis of Probable Alzheimer's Disease may qualify for a clinical trial to have three serial ExAblate BBB disruption procedures in specific areas in the brain. This study will be conducted at up to 8 sites in the United States and will enroll up to 30 patients.

Eligibility criteria: Inclusion Criteria:

1. Male or Female between 50-85 years of age
2. Probable Alzheimer's Disease (AD)
3. If taking concurrent Alzheimer's medication, has been on the medication for at least 2 months with a stable dose for at least 3 months
4. Able to communicate sensations during the ExAblate MRgFUS procedure
5. Ambulatory

Exclusion Criteria:

1. MRI Findings
2. Presence of unknown or MR unsafe devices anywhere in the body
3. Significant cardiac disease or unstable hemodynamic status
4. Relative contraindications to ultrasound contrast agent or PET amyloid tracer
5. History of a bleeding disorder
6. History of liver disease
7. Known cerebral or systemic vasculopathy
8. Significant depression and at potential risk of suicide
9. Any contraindications to MRI scanning
10. Any contraindication to lumbar puncture for collection of cerebral spinal fluid
11. Untreated, uncontrolled sleep apnea
12. History of seizure disorder or epilepsy
13. Severely Impaired renal function
14. Currently in a clinical trial involving an investigational product or non-approved use of a drug or device or in any other type of medical research
15. Chronic pulmonary disorders
16. Positive human immunodeficiency virus (HIV)
17. Known apolipoprotein E allele (ApoE4) homozygosity

Primary outcomes:
measure: Device and procedure related adverse events
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
measure: BBB Disruption and Closure
timeFrame: Immediately after the end of each ExAblate treatment and 24 hours post treatment
Locations:
city: Delray Beach
country: United States
facility: Delray Medical Center & Florida Atlantic University
state: Florida
city: Fort Lauderdale
country: United States
facility: Broward Health Medical Center & The University of Florida
state: Florida
city: Gainesville
country: United States
facility: University of Florida Health Shands
state: Florida
city: Miami
country: United States
facility: Baptist Health South Florida & Florida International University
state: Florida
city: Orlando
country: United States
facility: Advent Health
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Columbus
country: United States
facility: The Ohio State University -Wexner Medical Center
state: Ohio
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Morgantown
country: United States
facility: West Virginia University Rockefeller Neuroscience Center
state: West Virginia
Study officials:
References:
citation: Mathew AS, Gorick CM, Price RJ. Multiple regression analysis of a comprehensive transcriptomic data assembly elucidates mechanically- and biochemically-driven responses to focused ultrasound blood-brain barrier disruption. Theranostics. 2021 Oct 11;11(20):9847-9858. doi: 10.7150/thno.65064. eCollection 2021.
citation: Mehta RI, Carpenter JS, Mehta RI, Haut MW, Ranjan M, Najib U, Lockman P, Wang P, D'haese PF, Rezai AR. Blood-Brain Barrier Opening with MRI-guided Focused Ultrasound Elicits Meningeal Venous Permeability in Humans with Early Alzheimer Disease. Radiology. 2021 Mar;298(3):654-662. doi: 10.1148/radiol.2021200643. Epub 2021 Jan 5.