NCT02986932

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6

participants targeted

Target at below P25 for not_applicable alzheimer-disease

Timeline
Completed

Started Dec 2016

Shorter than P25 for not_applicable alzheimer-disease

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2016

Completed
5 days until next milestone

First Submitted

Initial submission to the registry

December 6, 2016

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 8, 2016

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2017

Completed
Last Updated

June 14, 2018

Status Verified

June 1, 2018

Enrollment Period

1 year

First QC Date

December 6, 2016

Last Update Submit

June 13, 2018

Conditions

Alzheimer Disease

Keywords

Blood-Brain Barrier

Outcome Measures

Primary Outcomes (1)

  • 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

    Immediately post treatment

Secondary Outcomes (7)

  • Change in amyloid uptake

    30 days after treatments

  • Adverse events

    90 days

  • MMSE - Mini Mental State Examination

    30 days

  • ADAS-Cog - Alzheimer's Disease Assessment Scale - Cognitive Behavior subscales

    30 days

  • NPI - Neuropsychiatry Inventory

    30 days

  • +2 more secondary outcomes

Study Arms (1)

BBB opening

EXPERIMENTAL

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.

Device: BBB opening

Interventions

BBB openingDEVICE

Open BBB using ExAblate focused ultrasound and (Definity®) contrast agent

BBB opening

Eligibility Criteria

Age55 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • +7 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Related Publications (1)

  • 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.

    PMID: 34815790DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Study Officials

  • Nir Lipsman, MD, PhD

    Sunnybrook Health Sciences Centre

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: Transcranial ExAblate
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 6, 2016

First Posted

December 8, 2016

Study Start

December 1, 2016

Primary Completion

December 1, 2017

Study Completion

December 1, 2017

Last Updated

June 14, 2018

Record last verified: 2018-06

Data Sharing

IPD Sharing
Will not share

Locations

CA(1)