Repeated Ultrasound Opening of the Blood-Brain Barrier in Amyotrophic Lateral Sclerosis

Who can take part

• Age 18-80 years,
• Able and willing to give signed and informed consent
• Confirmed diagnosis of ALS using the Gold Coast criteria with involvement of both upper and lower motor neurons in at least one body region, i.e. patients classified as "definite", "probable", "probable laboratory supported" or "possible" ALS using the El Escorial categories (patients with only lower motor neuron involvement will not be included)
• Disease duration <= 36 months,
• Mild functional impairment (ALSFRS-R ≥30),
• Change in ALSFRS-R score between 0.35 points and 1.1 points per month (both inclusive) in the period from onset of first symptoms to the Screening visit,
• Slow Vital capacity >= 70% of normal,
• If taking riluzole, patient on stable dose for over 30 days prior to study entry,
• Able and willing to follow trial procedures including site travels and visit requirements

Who cannot take part

• Patients with an uncontrolled intercurrent illness or any pre-existing comorbidities that in the Investigator's opinion may prevent the implantation of the device or may impair the ability of the patient to receive treatment with SonoCloud or may be cofounding for evaluation of the clinical trial
• Treatment with edaravone, tofersen or with another investigational drug or biological agent within 1 month or 5 half-lives of study agent, whichever is longer, before screening
• History or positive test result at screening for HIV, current hepatitis C infection (defined as positive HCV antibody and detectable HCV RNA) or current hepatitis B infection (defined as positive for HBsAg and/or total anti-HBc). Participants with positive HCV antibody and undetectable HCV RNA are eligible to participate in the study. Participants with immunity to hepatitis B from previous natural infection (defined as negative HbsAg, positive anti-HBc, and positive anti-HBs) or vaccination (defined as negative HbsAg, negative anti-HBc, and positive anti-HBs) are eligible to participate in the study
• Cardiac pacemaker (contraindication to MRI)
• Allergy to any drug used in the study (Gadolinium, Xylocain, Cloxacilline, EMLA, echographic contrast agent microbubbles: SonoVue®)
• Severe or instable chronic or acute disease or any life-threatening condition
• Other significant neurological or psychiatric disease in addition to ALS, including history of uncontrolled seizures
• Known severe pulmonary hypertension (pulmonary artery pressure >90 mmHg), uncontrolled systemic hypertension
• Known respiratory distress syndrome
• Invasive or non-invasive mechanical ventilation use
• Gastrostomy or nasogastric tube use
• Known right-to-left shunts,
• Women of child-bearing potential or sexually active man, without contraception
• Pregnant or breast-feeding woman
• Patient not affiliated or beneficiary of a social security category