Amyotrophic Lateral SclerosisNCT03321487
Blood-Brain Barrier Opening Using MR-Guided Focused Ultrasound in Patients With Amyotrophic Lateral Sclerosis
A study testing Blood-Brain Barrier opening with MRgFUS in people with Amyotrophic Lateral Sclerosis, run by InSightec at 1 site in Canada.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Blood-Brain Barrier opening with MRgFUS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteCanada
- Study dates
- 13 Apr 2018to 11 Sep 2023
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 35Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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).
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Blood-Brain Barrier opening with MRgFUS
- Keywords
- Blood-Brain Barrier disruption, Blood-Brain Barrier opening, magnetic resonance-guided focused ultrasound
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood-Brain Barrier opening with MRgFUSDevice
Also called Focused Ultrasound (FUS), Blood-Brain Barrier Disruption (BBBD), ExAblate MRgFUS
ExAblate Transcranial MR-guided Focused Ultrasound to temporarily open the Blood-Brain Barrier
| Study group | Role | What they receive |
|---|---|---|
| Stage I Cohort | Experimental | Blood-Brain Barrier opening with MRgFUS. BBB opening of a small volume of the primary motor cortex Receives: Device: Blood-Brain Barrier opening with MRgFUS |
| Stage II Cohort | Experimental | Blood-Brain Barrier opening with MRgFUS. BBB opening of a larger volume of the primary motor cortex Receives: Device: Blood-Brain Barrier opening with MRgFUS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety - Device and Procedure related adverse events
The number and severity of device and BBB opening procedure related adverse events will be evaluated.
Measured: At the time of the ExAblate MRgFUS procedure
Secondary outcomes (1)
Degree of contrast enhancement seen on post-procedure MRI
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.
Measured: At the time of the ExAblate MRgFUS procedure and 24 hours post-procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2017
- Study start13 Apr 2018
- Primary completion30 Dec 2021
- Study completion11 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by InSightecThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- InSightec
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lorne Zinman, MD, Principal investigator, Medical Director, ALS/Neuromuscular Clinic, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03321487
- Sponsor's protocol ID
- ALSFUS001
- Status last verified
- Mar 2026
- First submitted
- 23 Oct 2017
- Last updated
- 20 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03321487
- Acronym / sponsor ID
- ALSFUS001
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- Blood-Brain Barrier disruption, Blood-Brain Barrier opening, magnetic resonance-guided focused ultrasound
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- InSightecIndustry (pharma, biotech, devices)
- Study start
- 13 Apr 2018 (actual)
- Primary completion
- 30 Dec 2021 (actual)
- Study completion
- 11 Sep 2023 (actual)
- First posted
- 25 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stage I Cohort | Experimental | Device: Blood-Brain Barrier opening with MRgFUSBlood-Brain Barrier opening with MRgFUS. BBB opening of a small volume of the primary motor cortex |
| Stage II Cohort | Experimental | Device: Blood-Brain Barrier opening with MRgFUSBlood-Brain Barrier opening with MRgFUS. BBB opening of a larger volume of the primary motor cortex |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (35 listed)
- Unable to complete high-density CT and MRI studies of the head at the Screening Visit or any other MRI contraindication, such as:
- MRI findings:
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood-Brain Barrier opening with MRgFUSAlso: Focused Ultrasound (FUS), Blood-Brain Barrier Disruption (BBBD), ExAblate MRgFUSExAblate Transcranial MR-guided Focused Ultrasound to temporarily open the Blood-Brain Barrier | Device | Stage I Cohort, Stage II Cohort |
Primary outcome
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.
1 secondary outcome
Degree of contrast enhancement seen on post-procedure MRI
Time frame: At the time of the ExAblate MRgFUS procedure and 24 hours post-procedure
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lorne Zinman, MD principal investigator
Medical Director, ALS/Neuromuscular Clinic, Sunnybrook Health Sciences Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood-Brain Barrier opening with MRgFUS in people with Amyotrophic Lateral Sclerosis, 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 7 inclusion and 35 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 20 Mar 2026. 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?
Safety - Device and Procedure related adverse events (time frame: At the time of the ExAblate MRgFUS procedure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Mar 2026.