- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03321487
Blood-Brain Barrier Opening Using MR-Guided Focused Ultrasound in Patients With Amyotrophic Lateral Sclerosis
September 7, 2021 updated by: InSightec
Safety and Feasibility of Primary Motor Cortex Blood-Brain Barrier Opening Using Transcranial MR-Guided Focused Ultrasound With Intravenous Ultrasound Contrast Agent in Patients With Amyotrophic Lateral Sclerosis
The purpose of this study is to evaluate the safety, tolerability, and feasibility of Blood-Brain Barrier (BBB) opening using transcranial MRI-guided focused ultrasound in conjunction with an intravenous ultrasound contrast agent in patients with Amyotrophic Lateral Sclerosis (ALS).
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Anticipated)
8
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Ontario
-
Toronto, Ontario, Canada, M4N 3M5
- Sunnybrook Health Sciences Centre
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Diagnosed with laboratory supported probable, clinically probable or definite ALS according to the World Federation of Neurology Revised El Escorial criteria (Brooks et al. 2000).
- Right-hand dominant male or female aged 18 years or older.
- Capable of providing informed consent and complying with study procedures, including tolerability in the supine position and MRI examination without significant claustrophobia.
- If taking riluzole, on a stable dose for at least 30 days prior to Screening Visit.
- Slow Vital Capacity equal to or more than 50% predicted value for gender, height and age in the 30 days prior to the Screening Visit and able to lie supine without BiPAP.
- Severe left arm weakness and functional impairment, defined as Medical Research Council muscle strength score equals 3 or less in the index finger abduction and thumb abduction on the left side; OR severe left leg weakness and functional impairment, defined as Medical Research Council muscle strength score equals 3 or less at the hip flexors and ankle dorsiflexors on the left side.
- Able to communicate during the ExAblate® MRI-guided FUS procedure.
Exclusion Criteria:
Unable to complete high-density CT and MRI studies of the head at the Screening Visit or any other MRI contraindication, such as:
- Large body habitus and not fitting comfortably into the scanner
- Difficulty lying supine and still for up to 3 hours in the MRI unit or significant claustrophobia
MRI findings:
- Active infection/inflammation
- Acute or chronic brain hemorrhages, specifically lobar or subcortical microbleeds, 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.
Significant cardiac disease or unstable hemodynamic status including:
- Documented myocardial infarction within six months of enrollment
- Unstable angina on medication
- Unstable or worsening congestive heart failure
- Left ventricular ejection fraction below the lower limit of normal
- History of a hemodynamically unstable cardiac arrhythmia
- Cardiac or phrenic pacemaker
- Known right-to-left, bidirectional, or transient right-to-left cardiac shunt
- Patients with relative contraindications to perflutren including subjects with a family or personal history of QT prolongation or taking concomitant medications known to cause QTc prolongation,
- QT prolongation observed on screening ECG (QTc > 450 for men and >470 for women)
- Uncontrolled hypertension (systolic > 150 or diastolic BP > 100 on medication).
- On medications that increase the bleeding risk, specifically: a) aspirin or another antiplatelet medication (clopidogrel, prasugrel, ticlopidine, abciximab) for the last 7 days prior to treatment; b) oral, subcutaneous or intravenous anticoagulant medications, such as oral vitamin K inhibitors for the last 7 days, non-vitamin K inhibitor oral anticoagulant (dabigatran, apixaban, rivaroxaban) for the last 72 hours, and intravenous or subcutaneous heparin-derived compounds for the last 48 hours.
- History of a bleeding disorder, coagulopathy or a history of spontaneous hemorrhage.
- Known frontotemporal dementia.
- Abnormal coagulation profile, specifically: platelet <100,000/μl, Prothrombin Time >14 seconds, activated partial thromboplastin time (aPTT) >36 seconds, and INR > 1.3.
- Known cerebral or systemic vasculopathy, specifically cerebral amyloid angiopathy or systemic or central nervous system vasculitis.
- Known auto-immune condition with or without neurological manifestations (e.g., multiple sclerosis (MS), systemic lupus erythematous (SLE), Rheumatoid arthritis).
- Current or planned use of oral, intramuscular or intravenous steroid drugs (such as prednisone, prednisolone, dexamethasone, triamcinolone, methylprednisolone, oxandrolone, and others) or immunosuppressant drugs (azathioprine, mycophenolate, tacrolimus, sirolimus, cyclophosphamide, and others) for more than 7 days.
- Known sensitivity/allergy to gadolinium (an alternative product may be used), DEFINITY® contrast or any of its components.
- Untreated, uncontrolled sleep apnea.
- Impaired renal function with cystatin C-based estimated glomerular filtration rate <30 mL/min/1.73m2 and acute renal injury.
- Currently in a clinical trial involving an investigational product or non-approved use of a drug or device.
- Known respiratory diseases, specifically: chronic pulmonary disorders e.g., severe/uncontrolled COPD, pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area, asthma or hay fever.
- Patients with a history of drug allergies or multiple allergies where the benefit/risk of administering DEFINITY® is considered unfavorable by the study physicians in relation to the product monograph for DEFINITY®.
- Unqualified fit for the anesthesia by an anesthesiologist assessment, ASA I-III.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Stage I Cohort
Blood-Brain Barrier opening with MRgFUS.
BBB opening of a small volume of the primary motor cortex
|
ExAblate Transcranial MR-guided Focused Ultrasound to temporarily open the Blood-Brain Barrier
Other Names:
|
Experimental: Stage II Cohort
Blood-Brain Barrier opening with MRgFUS.
BBB opening of a larger volume of the primary motor cortex
|
ExAblate Transcranial MR-guided Focused Ultrasound to temporarily open the Blood-Brain Barrier
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety - Device and Procedure related adverse events
Time Frame: At the time of the ExAblate MRgFUS procedure
|
The number and severity of device and BBB opening procedure related adverse events will be evaluated.
|
At the time of the ExAblate MRgFUS procedure
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Degree of contrast enhancement seen on post-procedure MRI
Time Frame: At the time of the ExAblate MRgFUS procedure and 24 hours post-procedure
|
The extent and reversibility of BBB opening will be determined by the degree of contrast enhancement seen on post-procedure MRI with gadolinium-based contrast agent.
|
At the time of the ExAblate MRgFUS procedure and 24 hours post-procedure
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Lorne Zinman, MD, Medical Director, ALS/Neuromuscular Clinic, Sunnybrook Health Sciences Centre
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 13, 2018
Primary Completion (Anticipated)
December 30, 2021
Study Completion (Anticipated)
December 30, 2022
Study Registration Dates
First Submitted
October 23, 2017
First Submitted That Met QC Criteria
October 23, 2017
First Posted (Actual)
October 25, 2017
Study Record Updates
Last Update Posted (Actual)
September 8, 2021
Last Update Submitted That Met QC Criteria
September 7, 2021
Last Verified
January 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- ALSFUS001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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