Contrast-Enhanced Ultrasound for Spinal Cord Injury

Recruiting in Palo Alto (17 mi)

Overseen by Christoph Hofstetter, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of Washington

Disqualifiers: Head injury, Cardiopulmonary conditions, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

Patients with traumatic spinal cord injury (tSCI) often suffer from spinal cord swelling inside the thecal sac, which contains the spinal cord and surrounding fluid, leading to increased pressure on the spinal cord tissue and decreased spinal cord blood flow at the site of injury. The combination of increased pressure and decreased blood flow causes vascular hypoperfusion of the spinal cord and exacerbates the severity of injury. This is also referred to as secondary injury. Thus, knowledge of spinal cord hypoperfusion would allow the treating physician to optimize the hemodynamic condition of the patient with acute spinal cord injury and potentially improve functional outcomes.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Perflutren lipid, Definity, Luminity for spinal cord injury?

The research shows that contrast-enhanced ultrasound (CEUS) can effectively assess blood flow changes in spinal cord injuries, which is crucial for understanding and potentially improving treatment outcomes. Although the studies focus on imaging rather than direct treatment, they highlight the importance of monitoring blood flow to evaluate the severity of injury and the effectiveness of therapies. ^{1 2 3 4 5}

Is contrast-enhanced ultrasound generally safe for humans?

The research articles provided do not contain specific safety data for humans regarding contrast-enhanced ultrasound, but they do explore its use in animal models for spinal cord injury. ^{3 4 5 6 7}

How does the treatment Perflutren lipid differ from other treatments for spinal cord injury?

Perflutren lipid, used in contrast-enhanced ultrasound (CEUS), is unique because it allows for real-time imaging of blood flow changes in the spinal cord, which is not possible with other imaging techniques. This helps in assessing the severity of spinal cord injuries and monitoring the effects of treatments aimed at improving blood flow and reducing tissue damage. ^{1 2 3 4 5}

Research Team

Christoph Hofstetter, MD, PhD

Principal Investigator

University of Washington

Eligibility Criteria

This trial is for patients with traumatic spinal cord injury. It's aimed at those who have recently suffered from this condition and are experiencing swelling and pressure in the spinal area, which affects blood flow.

Inclusion Criteria

I am at least 18 years old.

I have had a spinal cord injury within the last 24 hours.

My spinal cord injury ranges from mild to complete loss of function below the injury.

Exclusion Criteria

My spinal cord injury is below the middle of my back.

Known sensitivity to lipid microsphere or its components, such as polyethylene glycol (PEG)

History of anaphylactoid reactions from ultrasound enhancing agents

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Surgery and Intraoperative Assessment

Routine surgery for decompression and stabilization of the spine, followed by contrast-enhanced ultrasound (CEUS) to assess blood flow at the site of injury

Immediate (during surgery)

1 visit (in-person, surgical)

Post-operative Follow-up

Participants receive routine MRI imaging within one week and one year post-surgery to monitor recovery and outcomes

1 year

2 visits (in-person)

Long-term Follow-up

Monitoring of chronic neurological outcomes and validation of CEUS biomarkers over a two-year period

2 years

Treatment Details

Interventions

• Perflutren lipid (Ultrasound Contrast Agent)

Trial Overview The study is testing Perflutren lipid, a contrast agent used in ultrasound imaging to visualize blood flow in the spinal cord after an acute injury. The goal is to optimize treatment by monitoring blood flow changes.

Participant Groups

Group I: Contrast-enhanced ultrasound in traumatic spinal cord injury Experimental Treatment 1 Intervention

A bolus IV injection of Perflutren lipid contrast agent will be given. Continuous imaging will be obtained.

Perflutren lipid is already approved in Canada for the following indications:

Approved in Canada as Definity for:

• Cardiovascular imaging
• Liver imaging

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Dr. Timothy H. Dellit

University of Washington

Chief Executive Officer since 2023

MD from University of Washington

Dr. Anneliese Schleyer

University of Washington

Chief Medical Officer since 2023

MD, MHA

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Pete Hegseth

United States Department of Defense

Chief Executive Officer

Bachelor's degree in Political Science from Princeton University, JD from Harvard Law School

Lisa Hershman

United States Department of Defense

Chief Medical Officer since 2021

MD from Uniformed Services University of the Health Sciences

Findings from Research

Real-time contrast enhanced ultrasound imaging (CEU) effectively assesses spinal cord blood flow (SCBF) changes in a rat model of spinal cord injury (SCI), providing a new method to evaluate neuroprotective therapies.

The study found critical ischemia at the injury epicenter 15 minutes post-SCI, while adjacent areas showed significantly reduced SCBF, highlighting the importance of targeting the ischemic penumbra zone for potential treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast enhanced ultrasound imaging for assessment of spinal cord blood flow in experimental spinal cord injury. Dubory, A., Laemmel, E., Badner, A., et al.[2018]

Ultrafast contrast-enhanced ultrasound (CEUS) imaging effectively visualizes and quantifies acute blood flow changes in a rat model of traumatic spinal cord injury, revealing significant loss of perfusion and structural alterations in the spinal vasculature immediately after injury.

CEUS demonstrated the ability to assess local tissue perfusion and blood flow velocities, suggesting its potential clinical application for determining the extent and severity of spinal cord injuries in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast-Enhanced Ultrasound for Assessment of Local Hemodynamic Changes Following a Rodent Contusion Spinal Cord Injury. Khaing, ZZ., Cates, LN., Hyde, J., et al.[2020]

Using contrast-enhanced ultrasound (CEUS) at higher frequencies (15 MHz) allows for improved imaging of blood flow changes in the spinal cord after injury, revealing significant differences in perfusion deficits between moderate and severe injuries in a rodent model.

The study found that acute blood flow changes, such as delayed microbubble arrival times and morphological alterations in blood vessels, correlate with chronic outcomes in locomotive function and the amount of spared spinal cord tissue, highlighting the potential of CEUS in assessing spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood Flow Changes Associated with Spinal Cord Injury Assessed by Non-linear Doppler Contrast-Enhanced Ultrasound. Bruce, M., DeWees, D., Harmon, JN., et al.[2023]

Contrast-enhanced ultrasound (CEUS) effectively quantifies spinal cord perfusion changes in a porcine model of acute spinal cord injury, revealing hypoperfusion at the injury site and hyperperfusion in adjacent areas.

The study demonstrated significant alterations in blood flow patterns post-injury, with CEUS providing valuable insights into microcirculatory changes that correlate with neurological function deterioration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative assessment of spinal cord perfusion by using contrast-enhanced ultrasound in a porcine model with acute spinal cord contusion. Huang, L., Lin, X., Tang, Y., et al.[2016]

This study utilized contrast-enhanced ultrasound (CEUS) to effectively measure spinal cord perfusion in rhesus monkeys with acute spinal cord injuries, revealing hypoperfusion at the injury epicenter and hyperperfusion in adjacent areas.

Quantitative analysis showed significant changes in perfusion parameters, with peak intensity decreasing at the injury site and increasing in surrounding regions, indicating that CEUS could be a valuable tool for real-time monitoring of spinal cord injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative contrast-enhanced ultrasonography for microcirculatory evaluation in rhesus monkey with spinal cord injury. Huang, L., Chen, K., Chen, FC., et al.[2018]

A modified fluorometric method using FITC-conjugated dextran effectively measures vascular permeability changes in rat spinal cord injury, demonstrating a reliable way to evaluate drug effects on this condition.

The study found that vascular injury, indicated by the vascular injury index (VII), increased with the severity of trauma, peaking at 2 hours post-injury, highlighting the method's sensitivity to changes in vascular permeability following spinal cord trauma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A sensitive fluorometric method for measurement of vascular permeability in spinal cord injury. Qu, ZX., Xu, J., Perot, PL., et al.[2016]

References

1. United States pubmed.ncbi.nlm.nih.gov

Contrast enhanced ultrasound imaging for assessment of spinal cord blood flow in experimental spinal cord injury. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Contrast-Enhanced Ultrasound for Assessment of Local Hemodynamic Changes Following a Rodent Contusion Spinal Cord Injury. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Blood Flow Changes Associated with Spinal Cord Injury Assessed by Non-linear Doppler Contrast-Enhanced Ultrasound. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Quantitative assessment of spinal cord perfusion by using contrast-enhanced ultrasound in a porcine model with acute spinal cord contusion. [2016]

5. United States pubmed.ncbi.nlm.nih.gov

Intraoperative contrast-enhanced ultrasonography for microcirculatory evaluation in rhesus monkey with spinal cord injury. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Dynamic Contrast-Enhanced MR Perfusion of Intradural Spinal Lesions. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

A sensitive fluorometric method for measurement of vascular permeability in spinal cord injury. [2016]