Blood-Brain Barrier Opening Using MR-Guided Focused Ultrasound in Patients With Amyotrophic Lateral Sclerosis

NCT03321487 | Completed DMC

• 1 other identifier: ALSFUS001
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Blood-Brain Barrier disruption; Blood-Brain Barrier opening; magnetic resonance-guided focused ultrasound

Outcome Measures

Primary Outcomes (1)

• Safety - Device and Procedure related adverse events

  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 Outcomes (1)

• Degree of contrast enhancement seen on post-procedure MRI

  At the time of the ExAblate MRgFUS procedure and 24 hours post-procedure

Study Arms (2)

Stage I Cohort

EXPERIMENTAL

Blood-Brain Barrier opening with MRgFUS. BBB opening of a small volume of the primary motor cortex

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

Device: Blood-Brain Barrier opening with MRgFUS

Interventions

Blood-Brain Barrier opening with MRgFUS DEVICE

ExAblate Transcranial MR-guided Focused Ultrasound to temporarily open the Blood-Brain Barrier

Also known as: Focused Ultrasound (FUS), Blood-Brain Barrier Disruption (BBBD), ExAblate MRgFUS

Stage I Cohort; Stage II Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• InSightec: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Lorne Zinman, MD

  Medical Director, ALS/Neuromuscular Clinic, Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2017
• First Posted: October 25, 2017
• Study Start: April 13, 2018
• Primary Completion: December 30, 2021
• Study Completion: September 11, 2023
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)