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Alzheimer DiseaseBBB-AlzheimersNCT02986932

Blood-Brain-Barrier Opening Using Focused Ultrasound With IV Contrast Agents in Patients With Early Alzheimer's Disease

A study testing BBB opening in people with Alzheimer Disease, run by InSightec at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 55 to 85 years
Conditions the study is for
Alzheimer Disease
What is being tested?
BBB opening
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteCanada
Study dates
Dec 2016to Dec 2017
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 22Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

Other trials in Canada

About this study

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

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.

Read the 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.

Being tested
BBB opening
Keywords
Blood-Brain Barrier
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BBB openingDevice

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

Study groups in NCT02986932
Study groupRoleWhat they receive
BBB openingExperimentalExAblate 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.
Receives: Device: BBB opening

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Immediately post treatment

Secondary outcomes (7)

  1. Change in amyloid uptake

    Change in amyloid uptake as compared to pre treatment scans in the targeted region

    Measured: 30 days after treatments

  2. Adverse events

    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Measured: 90 days

  3. MMSE - Mini Mental State Examination

    Treatment effect on patients' dementia state

    Measured: 30 days

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

    Treatment effect on patients' Alzheimer's disease symptoms

    Measured: 30 days

  5. NPI - Neuropsychiatry Inventory

    Treatment effect on patients' dementia

    Measured: 30 days

  6. GDS - Geriatric Depression Scale

    Treatment effect on patients' depression

    Measured: 30 days

  7. ADCS-ADL - Alzheimer's Disease Co-operative Study - Activities of Daily Living Inventory

    Treatment effect on patients' activities of daily living

    Measured: 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Dec 2016 (estimated)
  2. Study startDec 2016
  3. Primary completionDec 2017
  4. Study completionDec 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Transcranial ExAblate
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02986932
Sponsor's protocol ID
AL001
Acronym
BBB-Alzheimers
Status last verified
Jun 2018
First submitted
6 Dec 2016
Last updated
14 Jun 2018
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 34815790

Questions about this trial

What is this clinical trial studying?

A study testing BBB opening in people with Alzheimer Disease, run by InSightec at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in contrast enhancement (intensity) following BBB disruption (time frame: Immediately post treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02986932, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2018.

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