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Trial record 63 of 681 for:    amyotrophic lateral sclerosis

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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03321487
Recruitment Status : Active, not recruiting
First Posted : October 25, 2017
Last Update Posted : July 12, 2019
Sponsor:
Information provided by (Responsible Party):
InSightec

Tracking Information
First Submitted Date  ICMJE October 23, 2017
First Posted Date  ICMJE October 25, 2017
Last Update Posted Date July 12, 2019
Actual Study Start Date  ICMJE April 13, 2018
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 23, 2017)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03321487 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 30, 2017)
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2017)
Feasibility of BBB opening in ALS [ 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Blood-Brain Barrier Opening Using MR-Guided Focused Ultrasound in Patients With Amyotrophic Lateral Sclerosis
Official Title  ICMJE 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
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Amyotrophic Lateral Sclerosis
Intervention  ICMJE Device: Blood-Brain Barrier opening with MRgFUS
ExAblate Transcranial MR-guided Focused Ultrasound to temporarily open the Blood-Brain Barrier
Other Names:
  • Focused Ultrasound (FUS)
  • Blood-Brain Barrier Disruption (BBBD)
  • ExAblate MRgFUS
Study Arms  ICMJE
  • Experimental: Stage I Cohort
    Blood-Brain Barrier opening with MRgFUS. BBB opening of a small volume of the primary motor cortex
    Intervention: Device: Blood-Brain Barrier opening with MRgFUS
  • Experimental: Stage II Cohort
    Blood-Brain Barrier opening with MRgFUS. BBB opening of a larger volume of the primary motor cortex
    Intervention: Device: Blood-Brain Barrier opening with MRgFUS
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: October 23, 2017)
8
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 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).
  2. Right-hand dominant male or female aged 18 years or older.
  3. Capable of providing informed consent and complying with study procedures, including tolerability in the supine position and MRI examination without significant claustrophobia.
  4. If taking riluzole, on a stable dose for at least 30 days prior to Screening Visit.
  5. 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.
  6. 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.
  7. Able to communicate during the ExAblate® MRI-guided FUS procedure.

Exclusion Criteria:

  1. 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
  2. MRI findings:

    • Active infection/inflammation
    • Acute or chronic brain hemorrhages, specifically lobar or subcortical microbleeds, siderosis or macrohemorrhages
    • Tumor/space occupying lesion
    • Meningeal enhancement
  3. 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.
  4. Clips or other metallic implanted objects in the skull or the brain, except shunts.
  5. 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)
  6. Uncontrolled hypertension (systolic > 150 or diastolic BP > 100 on medication).
  7. 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.
  8. History of a bleeding disorder, coagulopathy or a history of spontaneous hemorrhage.
  9. Known frontotemporal dementia.
  10. Abnormal coagulation profile, specifically: platelet <100,000/μl, Prothrombin Time >14 seconds, activated partial thromboplastin time (aPTT) >36 seconds, and INR > 1.3.
  11. Known cerebral or systemic vasculopathy, specifically cerebral amyloid angiopathy or systemic or central nervous system vasculitis.
  12. Known auto-immune condition with or without neurological manifestations (e.g., multiple sclerosis (MS), systemic lupus erythematous (SLE), Rheumatoid arthritis).
  13. 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.
  14. Known sensitivity/allergy to gadolinium (an alternative product may be used), DEFINITY® contrast or any of its components.
  15. Untreated, uncontrolled sleep apnea.
  16. Impaired renal function with cystatin C-based estimated glomerular filtration rate <30 mL/min/1.73m2 and acute renal injury.
  17. Currently in a clinical trial involving an investigational product or non-approved use of a drug or device.
  18. 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.
  19. 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®.
  20. Unqualified fit for the anesthesia by an anesthesiologist assessment, ASA I-III.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03321487
Other Study ID Numbers  ICMJE ALSFUS001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party InSightec
Study Sponsor  ICMJE InSightec
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lorne Zinman, MD Medical Director, ALS/Neuromuscular Clinic, Sunnybrook Health Sciences Centre
PRS Account InSightec
Verification Date July 2019

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