Intravenous Immunoglobulin (IVIG) and Blood-Brain Barrier Disruption in Amyotrophic Lateral Sclerosis (ALS)

NCT07193953 | Recruiting Phase 1

• 1 other identifier: 6271
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to evaluate the safety and feasibility of IVIg administration in conjunction with primary motor cortex BBB opening using the Next Generation Dome Helmet (NGDH) FUS in adult participants with ALS.

Conditions

Amyotrophic Lateral Sclerosis; ALS

Keywords

ALS; Focused Ultrasound; Blood Brain Barrier Opening; Intravenous Immunoglobulin; Motor Neuron Disease

Outcome Measures

Primary Outcomes (4)

• Safety of IVIg in patients with ALS

  This will be assessed up through the incidence of drug-related adverse events, serious adverse events, and discontinuations due to adverse events after Intravenous Immunoglobulin (IVIg) administration.

  During and after IVIg administration at Week 0 and Week 2 Day 1 until Week 24.

• Safety of DEFINITY® microbubbles

  This will be assessed up through the incidence of drug-related adverse events, serious adverse events, and discontinuations due to adverse events after DEFINITY® infusion during focused ultrasound (FUS) blood brain barrier (BBB) opening.

  During and after DEFINITY® administration at Week 2 Day 1 until Week 24.

• Feasibility of FUS BBB opening in the motor cortex

  This will be measured as detectable gadolinium enhancement at the arm, leg and bulbar regions of the motor cortex bilaterally following FUS with posterior normalization.

  During and after Week 2 Day 1 FUS BBB opening until Week 24.

• Safety of FUS BBB opening in the motor cortex

  Incidence of BBB opening-related and FUS-related adverse events, serious adverse events, incidence of asymptomatic or symptomatic radiologic complication, such as evidence of bleeding or swelling after FUS, incidence of electrographic complication, such as epileptiform discharges on EEG, or accelerated ALS disease progression, defined as ≥ 6-point decline in the ALSFRS-R scores from Baseline to week 8.

  From up to 30 days before Week 0 to Week 24.

Secondary Outcomes (2)

• Neurofilament light chain (NfL) levels in blood plasma and cerebrospinal fluid

  From up to 30 days before Week 0 to Week 24.

• Inflammatory markers in blood and cerebrospinal fluid

  From up to 30 days before Week 0 to Week 24.

Other Outcomes (4)

• Pharmacokinetics Outcome - Immunoglobulin G Concentration

  From up to 30 days before Week 0 to Week 24.

• Exploratory Outcomes - ALSFRS-R scores

  From up to 30 days before Week 0 to Week 24.

• Exploratory Outcomes - Changes in levels of cerebral chemicals measured using Magnetic Resonance Spectroscopy

  From up to 30 days before Week 0 to Week 24.

Study Arms (1)

Intravenous Immunoglobulin Administration using Focused Ultrasound

EXPERIMENTAL

ALS patients will be assigned to receive Intravenous Immunoglobulin (IVIg) and DEFINITY® microbubbles. The first three enrolled patients will participate in the first cohort, receiving 0.4g/kg divided in two doses. After a preliminary safety assessment of the first cohort, the next three successfully screened patients will be enrolled in the second cohort, receiving 0.8g/kg divided in two doses. The second IVIg dose in each cohort will be administered in combination with Next Generation Dome Helmet (NGDH) focused ultrasound (FUS) to transiently open the blood-brain barrier and enhance IVIg delivery to the primary motor cortex.

Device: Next Generation Dome Helmet Focused Ultrasound; Drug: Intravenous immunoglobulin (IVIG), 10% solution for infusion; Drug: Definity® Vial for (Perflutren Lipid Microsphere) Injectable Suspension

Interventions

Next Generation Dome Helmet Focused Ultrasound DEVICE

Two doses of IVIg will be administered 2 weeks apart. The first dose at Week 0 will be a standalone administration. The second dose at Week 2 will be combined with Next Generation Dome Helmet (NGDH) Focused Ultrasound (FUS) blood brain barrier (BBB) opening.

Intravenous Immunoglobulin Administration using Focused Ultrasound

Intravenous immunoglobulin (IVIG), 10% solution for infusion DRUG

Two doses of IVIg will be administered 2 weeks apart. The first dose at Week 0 will be a standalone administration. The second dose at Week 2 will be combined with Next Generation Dome Helmet (NGDH) Focused Ultrasound (FUS) blood brain barrier (BBB) opening. Cohort I will receive 0.2g/kg of IVIg at each dose. Cohort II will receive 0.4g/kg of IVIg at each dose. Privigen® IVIg comes in vials containing 10% active ingredient. It is supplied in 2.5 g (25 mL bottle), 5 g (50 mL bottle), 10 g (100 mL bottle), 20 g (200 mL bottle) or 40 g (400 mL bottle). The IVIg dose will be determined based on the patient's ideal body weight.

Intravenous Immunoglobulin Administration using Focused Ultrasound

Definity® Vial for (Perflutren Lipid Microsphere) Injectable Suspension DRUG

DEFINITY® Perflutren Injectable Microbubbles is an ultrasound contrast imaging agent that will be used for blood brain barrier opening during focused ultrasound. These microbubbles will be injected during the focused ultrasound procedure on the day of the second IVIg dose.

Intravenous Immunoglobulin Administration using Focused Ultrasound

Eligibility Criteria

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

You may qualify if:

• Diagnosed with ALS as per the Gold Coast Criteria;
• Aged 18 years or older;
• Capable of providing informed consent and complying with study procedures;
• If taking Riluzole, on a stable dose for at least 4 weeks prior to Baseline;
• If taking Edaravone, on a stable dose of one completed cycle prior to Baseline;
• Respiratory Function Criterion:
• Able to lie supine without BiPAP or breathing discomfort; OR
• Forced vital capacity or slow vital capacity ≥50% of the predicted value for sex, height and age, if available
• Able to communicate sensations during the Dome FUS procedure.
• Qualified fit for the anesthesia by an anesthesiologist, ASA I-III.

You may not qualify if:

• MRI findings:
• Active infection/inflammation
• Acute or chronic hemorrhages, specifically \> 4 lobar microbleeds, and no siderosis or macrohemorrhages
• Tumor/space occupying lesion causing significant mass effect
• Meningeal enhancement
• Intracranial hypotension
• 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 screening
• 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 pacemaker

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Focused Ultrasound Foundation: collaborator

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Interventions

Immunoglobulins, Intravenous; Solutions

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pharmaceutical Preparations

Central Study Contacts

Nir Lipsman, MD, PhD, FRCPC

CONTACT

(416) 480-6100; alsresearch@sunnybrook.ca

Caroline Giuricich, MSc

CONTACT

(416) 480-6100; caroline.giuricich@sri.utoronto.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Hurvitz Brain Sciences Program, Director of Harquail Centre for Neuromodulation, Director of Neurosurgery Residency Program, Principal Investigator, Associate Professor

Model Details: The first cohort (n = 3) will receive 0.4g/kg of IVIg, divided into two 0.2g/kg doses. After a preliminary safety and tolerability assessment of the first cohort, patients will be enrolled to the second cohort (n = 3). It will follow the same design but with 0.8g/kg divided into two 0.4g/kg doses.

Study Record Dates

• First Submitted: May 12, 2025
• First Posted: September 26, 2025
• Study Start: April 15, 2025
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): May 30, 2027
• Last Updated: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)