Contrast-Enhanced Ultrasound for Hydrocephalus

Overseen By Maria Mezher, MD

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital of Philadelphia

Disqualifiers: Lumason hypersensitivity, Hemodynamic instability, Respiratory instability

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new method for assessing brain health in babies with hydrocephalus, a condition where fluid accumulates in the brain. Instead of the usual invasive treatments, the study uses a special type of ultrasound with a contrast agent, specifically Sulfur Hexafluoride Lipid Type A Microspheres, to evaluate its safety and practicality. Babies eligible for the trial have been diagnosed with or are suspected to have hydrocephalus and are patients at the Children's Hospital of Philadelphia. This approach could provide a less invasive way to monitor the condition in these young patients. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

What prior data suggests that this contrast-enhanced ultrasound is safe for neonates and infants with hydrocephalus?

Research shows that sulfur hexafluoride lipid-type A microspheres, used in contrast-enhanced ultrasound (CEUS), are generally safe. These tiny bubbles have been used in many ultrasound exams with very few reported side effects. The FDA's reports on Lumason, the product name, confirm this. Most patients tolerate it well.

In this study, CEUS is being used to check for hydrocephalus in infants. The procedure is non-invasive, meaning it doesn't involve surgery, and includes a short monitoring period after the ultrasound. The safety of this treatment in other applications suggests it could be safe for this purpose as well. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using contrast-enhanced ultrasound (CEUS) for hydrocephalus because it offers a non-invasive way to get a detailed look at the brain's ventricles. Unlike traditional imaging methods like CT scans or MRIs, which can be costly and time-consuming, CEUS uses Sulfur Hexafluoride Lipid Type A microspheres to enhance ultrasound images quickly and safely. This technique allows for real-time imaging without the need for radiation exposure, making it a safer option for repeated monitoring. By potentially providing clearer and faster results, CEUS could revolutionize how doctors diagnose and manage hydrocephalus.

What evidence suggests that contrast-enhanced ultrasound is effective for hydrocephalus?

Research has shown that Sulfur Hexafluoride Lipid Type A Microspheres work well as a contrast agent in ultrasound scans. They enhance ultrasound images, allowing doctors to see inside the body more clearly. This is particularly beneficial for children, as it has been successfully used in pediatric patients. Although specific data on its use for hydrocephalus is limited, the agent's ability to improve imaging suggests it could aid doctors in making better treatment decisions for this condition. In this trial, participants will undergo brain contrast-enhanced ultrasound using this agent. Its approval for other uses supports its general safety and effectiveness. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for newborns and infants diagnosed with or suspected to have hydrocephalus, which is a condition where fluid builds up in the brain. It's important that participants haven't had previous treatments that could interfere with the study.

Inclusion Criteria

Inpatients at the Children's Hospital of Philadelphia

Parental/Legally authorized representative permission

My child is under 1.5 years old and may have hydrocephalus.

Exclusion Criteria

Hemodynamic instability as defined by rapid escalation of cardiopulmonary support in the past 12-24 hours, as defined by the clinical care team

Medical history of Lumason hypersensitivity

My breathing support needs have quickly increased recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

CEUS Examination

Participants undergo brain contrast-enhanced ultrasound (CEUS) to assess safety and feasibility

1-2 weeks

Up to 2 visits (in-person)

Monitoring

Participants are monitored for 60 minutes post-CEUS and for adverse events up to 48 hours post-scanning

48 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sulfur Hexafluoride Lipid Type A Microspheres

Trial Overview The trial tests if a special ultrasound using Sulfur Hexafluoride Lipid microspheres can safely assess brain health in babies with hydrocephalus, potentially offering an alternative to current invasive methods.

How Is the Trial Designed?

Group I: Brain contrast-enhanced ultrasound Experimental Treatment 1 Intervention

The study duration per subject will be up to 30 minutes including the time to prepare the contrast agent, perform the pre-contrast imaging and the contrast-enhanced ultrasound (CEUS), as well as the 60-minute monitoring period after the administration of the contrast agent. A second CEUS exam may be performed within 1-2 weeks from the first scan for up to two CEUS exams of 1 hour and 30-minute duration each. Study participation will be complete when the 60-minute monitoring period of the last CEUS performed is complete.

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

Published Research Related to This Trial

A study analyzing the FDA Adverse Event Reporting System found no significant new safety concerns or major cardiovascular events associated with perflutren ultrasound contrast agents, reinforcing their relative cardiovascular safety.

The most reported adverse events were back pain and flank pain, but these were not linked to serious cardiovascular issues, suggesting that while some discomfort may occur, the overall safety profile remains favorable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Perflutren Ultrasound Contrast Agents: A Disproportionality Analysis of the US FAERS Database. Hauben, M., Hung, EY., Hanretta, KC., et al.[2018]

Contrast-enhanced ultrasound (CEUS) using sulfur hexafluoride is safe for use in pediatric patients, as demonstrated in a study involving 173 children with a mean age of 11 years.

The study included a total of 287 CEUS exams, indicating a robust evaluation of the safety of this imaging technique in a diverse age range from 0.1 to 18 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corrigendum. [2019]

The study demonstrated that a perfluorochemical stabilized microbubble-based ultrasound contrast agent significantly enhances color-Doppler-amplitude and gray-scale imaging of cerebral blood flow (CBF) in dogs, indicating its potential effectiveness for visualizing blood flow in the brain.

The results showed a strong correlation between the ultrasound intensity changes and regional CBF, suggesting that this method could be a valuable noninvasive tool for evaluating CBF, particularly in critically ill newborns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of regional cerebral blood flow in dogs, with an experimental microbubble-based US contrast agent. Greenberg, RS., Taylor, GA., Stapleton, JC., et al.[2015]

The study developed new microbubbles using lipids and sulfur hexafluoride (SF6) that significantly enhance the echogenicity of thrombi, improving their visibility during ultrasound imaging.

These targeted microbubbles demonstrated high stability and maintained their characteristics for up to 8 hours, providing a longer diagnostic window compared to traditional nontargeted microbubbles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonging the ultrasound signal enhancement from thrombi using targeted microbubbles based on sulfur-hexafluoride-filled gas. Wang, B., Zang, WJ., Wang, M., et al.[2016]

Lipid-coated microbubbles can enhance ultrasound imaging of brain tumors, allowing for earlier detection of gliomas in rats, with a significant reduction in time to visual detection from 6.67 days to 4.09 days when injected daily.

These microbubbles are stable for at least 6 months in vitro and have a half-life of over 20 hours in vivo, making them a promising contrast agent for intraoperative neurosonology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid-coated uniform microbubbles for earlier sonographic detection of brain tumors. D'Arrigo, JS., Simon, RH., Ho, SY.[2019]

The novel ultrasound contrast agent BR 14 significantly enhances signal intensity in the brain parenchyma, with a mean increase of +61% at a lower dose (0.05 ml/kg) and +24% at a higher dose (0.2 ml/kg) in a study involving six sedated beagle dogs.

Higher doses of BR 14 can lead to a paradoxical 'shadowing effect,' where increased signal intensity near the ultrasound probe results in decreased visibility of structures further away, demonstrating the importance of dose selection in ultrasound imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Harmonic imaging of the brain parenchyma using a perfluorobutane-containing ultrasound contrast agent. Seidel, G., Meyer, K., Algermissen, C., et al.[2019]

In a large study of 463,434 contrast-enhanced ultrasound examinations, the use of sulfur hexafluoride microbubbles resulted in a very low adverse event (AE) frequency of only 0.034%, indicating a high safety profile for this contrast agent.

Among the reported AEs, only 4 were classified as serious, and the majority were non-serious, with most reactions occurring within 30 minutes of administration, confirming that sulfur hexafluoride microbubbles are safe for routine clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety findings after intravenous administration of sulfur hexafluoride microbubbles to 463,434 examinations at 24 centers. Shang, Y., Xie, X., Luo, Y., et al.[2023]

In a study involving 167 contrast-enhanced ultrasound examinations in 137 children with oncologic diseases, only one severe anaphylactic reaction (0.6%) was reported, indicating a generally favorable safety profile for intravenous second-generation ultrasound contrast agents containing sulfur hexafluoride.

No other adverse events were observed, such as changes in vital signs or common side effects like flushing or nausea, suggesting that these agents are well-tolerated in pediatric patients, although ongoing monitoring for potential reactions is recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of intravenous application of second-generation ultrasound contrast agent in children: prospective analysis. Piskunowicz, M., Kosiak, W., Batko, T., et al.[2022]

Lipid-shelled microbubbles used for focused ultrasound (FUS) to open the blood-brain barrier (BBB) remain stable for up to 3 weeks post-activation, maintaining their therapeutic efficacy despite a natural decay in concentration.

In a mouse model, BBB opening achieved with these microbubbles showed consistent volume and contrast enhancement over 21 days, indicating that the microbubbles can effectively facilitate drug delivery into the brain without significant loss of performance over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporal stability of lipid-shelled microbubbles during acoustically-mediated blood-brain barrier opening. Pouliopoulos, AN., Jimenez, DA., Frank, A., et al.[2021]

Microbubbles (MBs) made with perfluoropropane and perfluorobutane showed better stability for ultrasound imaging and more effective drug delivery to the brain compared to those made with sulfur hexafluoride, based on in vitro and in vivo assessments.

The use of these gas-loaded MBs did not cause significant damage to brain tissue, indicating their potential safety for therapeutic applications in drug delivery systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of encapsulated gas on stability of lipid-based microbubbles and ultrasound-triggered drug delivery. Omata, D., Maruyama, T., Unga, J., et al.[2020]

In a study of 173 children who underwent 287 contrast-enhanced ultrasound (CEUS) exams using sulfur hexafluoride microbubbles, no immediate adverse effects were reported, suggesting that CEUS is safe for use in pediatric patients.

The study indicates that CEUS can be effectively used for various indications in children, including assessing liver conditions, without significant safety concerns, challenging the current restrictions on its use in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast-enhanced ultrasound using sulfur hexafluoride is safe in the pediatric setting. Torres, A., Koskinen, SK., Gjertsen, H., et al.[2018]

Gas-filled microbubbles, specifically custom-made albumin-coated microbubbles and SonoVue, have shown promising results as MR contrast agents in brain imaging, with similar transverse relaxation rate enhancements observed in a study involving 5 Sprague-Dawley rats.

These microbubbles can potentially enable real-time MRI guidance for drug delivery and therapeutic applications in the central nervous system, highlighting their biocompatibility and effectiveness in enhancing imaging contrast.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbubbles as a novel contrast agent for brain MRI. Cheung, JS., Chow, AM., Guo, H., et al.[2015]

Citations

1. fda.gov fda.gov/media/103029/download

Statistical Review and Evaluation Sulfur Hexafluoride ... This reviewer independent analysis is supportive of the efficacy and safety of the use of Lumason for VUS in pediatric patients. 5.2.

2. synapse.patsnap.com synapse.patsnap.com/drug/3e26f8deaef14a55ab890f5cf817f276

Sulfur Hexafluoride - Drug Targets, Indications, Patents Sulfur Hexafluoride: a Ultrasonography enhancers Drug, Initially developed by Bracco International BV, Now, its global highest R&D status is Approved, ...

3. fda.gov fda.gov/media/133813/download

CLINICAL REVIEW Lumason (sulfur hexafluoride lipid-type A microspheres). 1. CLINICAL ... The totality of the efficacy data from adult and pediatric studies of ...

4. researchgate.net researchgate.net/publication/354286338_Efficacy_of_a_phospholipid-stabilized_sulfur_hexafluoride_microsphere_contrast_agent_and_water_for_hydrosonography_of_the_upper_portion_of_the_gastrointestinal_tract_in_dogs

Efficacy of a phospholipid-stabilized sulfur hexafluoride ... Objective: To investigate the efficacy of a phospholipid-stabilized sulfur hexafluoride microsphere (SHM) contrast agent and water for ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11562123/

The CSF lipid profile in patients with probable idiopathic ... We detected no difference in the CSF lipid profile between probable idiopathic normal pressure hydrocephalus patients with and without clinical improvement ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06693752

CEUS Evaluation of Hydrocephalus in Neonates and ... Hydrocephalus affects up to 2 out of every 500 births and results in long-term disability in up to 78% of those affected. The standard treatment of ...

7. fda.gov fda.gov/media/181813/download

Lumason Pediatric Postmarketing Safety Review This review evaluates FDA Adverse Event Reporting System (FAERS) reports for Lumason. (sulfur hexafluoride lipid-type A microspheres) in ...

8. ctv.veeva.com ctv.veeva.com/study/ceus-evaluation-of-hydrocephalus-in-neonates-and-infants

CEUS Evaluation of Hydrocephalus in Neonates and Infants Hydrocephalus affects up to 2 out of every 500 births and results in long-term disability in up to 78% of those affected.

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40815859/

Outcomes of ventriculoperitoneal shunt surgery for ... This review provides a comprehensive profile of VPS complications and outcomes in pediatric patients in LMICs. Despite a predominance of ...

10. withpower.com withpower.com/trial/phase-2-hydrocephalus-in-infants-10-2024-be0c9

Contrast-Enhanced Ultrasound for Hydrocephalus Sulfur hexafluoride microbubble contrast agents have been used in a large number of ultrasound exams and are generally considered safe, with very few adverse ...