ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02986932
Recruitment Status : Recruiting
First Posted : December 8, 2016
Last Update Posted : March 28, 2017
Sponsor:
Information provided by (Responsible Party):
InSightec

December 6, 2016
December 8, 2016
March 28, 2017
December 2016
December 2017   (Final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT02986932 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
Blood-Brain-Barrier Opening Using Focused Ultrasound With IV Contrast Agents in Patients With Early Alzheimer's Disease
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.
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.
Interventional
Not Applicable
Intervention Model: Single Group Assignment
Intervention Model Description:
Transcranial ExAblate
Masking: None (Open Label)
Primary Purpose: Treatment
Alzheimer Disease
Device: BBB opening
Open BBB using ExAblate focused ultrasound and (Definity®) contrast agent
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.
Intervention: Device: BBB opening
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
6
Same as current
December 2017
December 2017   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Probable AD consistent with NIA/AA criteria (McKhann, Alzheimer & Dementia 2011)
  2. Modified Hachinski Ischemia Scale (MHIS) score of <= 4.
  3. Mini Mental State Exam (MMSE) scores 18-28
  4. Short form Geriatric Depression Scale (GDS) score of <= 6
  5. Has a Florbetaben PET scan consistent with the presence of amyloid pathology in the proposed target region (right frontal lobe)
  6. Able to communicate sensations during the ExAblate® MRgFUS procedure.

Exclusion Criteria:

  1. MRI findings:

    • Active infection/inflammation
    • Acute or chronic hemorrhages, specifically > 4 lobar microbleeds, and no siderosis or macrohemorrhages
    • Tumor/space occupying lesion
    • Meningeal enhancement
  2. 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
  3. Clips or other metallic implanted objects in the skull or the brain, except shunts; other metallic objects implanted in body
  4. Significant cardiac disease or unstable hemodynamic status including:
  5. Uncontrolled hypertension on medication or abnormal ECG
  6. 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
  7. History of a bleeding disorder, coagulopathy or a history of spontaneous hemorrhage or use of anticoagulants
  8. Abnormal coagulation profile (PLT < 100,00/μl), PT (>14 sec) or PTT (>36 sec), and INR > 1.3
  9. No more than 1 non-strategic lacune <1.5 cm
  10. Known cerebral or systemic vasculopathy
  11. Significant depression and at potential risk of suicide
  12. Known sensitivity/allergy to gadolinium (an alternative product may be used), Definity or any of its components.
  13. Any contraindications to MRI scanning such as metallic implants, claustrophibia or too large for MRI scanner
  14. Untreated, uncontrolled sleep apnea
  15. Impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2
  16. 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
  17. 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.
  18. Currently in a clinical teial involving investigational product.
Sexes Eligible for Study: All
55 Years to 85 Years   (Adult, Senior)
No
Canada
 
 
NCT02986932
AL001
Yes
Not Provided
Plan to Share IPD: No
InSightec
InSightec
Not Provided
Principal Investigator: Nir Lipsman, MD, PhD Sunnybrook Health Sciences Centre
InSightec
March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP