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

ConditionsAmyotrophic Lateral Sclerosis ALS

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18+

SponsorSunnybrook Health Sciences Centre

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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;

Disqualifiers

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

Trial design

Design model

Sequential

Treatments tested in this trial

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 (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.
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.

Treatment groups

6 Participants

are divided into 1 treatment group

Group A: Intravenous Immunoglobulin Administration using Focused UltrasoundExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

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.

Time frame

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.

Time frame

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.

Time frame

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.

Time frame