Contrast-enhanced Ultrasound as a Screening Tool for Kidney Cancer in Patients With Von-Hippel Lindau (CEUS-VHL)

Double-Center Cross-Sectional Study of Contrast-Enhanced Ultrasound With Lumason/Definity as a Screening Tool for Kidney Cancer in Patients With Von-Hippel Lindau

The purpose of this study is to determine if contrast-enhanced ultrasound can detect abnormal features of kidney lesions in patients with Von-Hippel Lindau with the same accuracy as conventional ultrasound and contrast-enhanced magnetic resonance imaging (MRI)

Study Overview

• Status: Completed
• Conditions: Kidney Disease, Chronic; Von-Hippel Lindau
• Intervention / Treatment: Drug: Perflutren lipid microsphere; Drug: Sulfur hexafluoride lipid microspheres

Detailed Description

This is a pilot cross-sectional study that compares contrast enhanced ultrasound to conventional ultrasound and contrasted MRI. Any patient undergoing annual imaging screening is eligible, but the investigators will target inclusion of at least 10 subjects who have at least 1 kidney lesion. Therefore, up to 5 subjects may have no current kidney lesions. Subject participation will be only for the day of CEUS study. There will be no follow-up period for this study. However, if results are encouraging, a longitudinal observational study may follow, and these same subjects would be eligible for enrollment. Eligible subjects will undergo a contrast enhanced ultrasound.

Following completion of imaging, all CEUS, MRI (within 4 months) and B-mode (at time of CEUS) US studies will be de-identified. Blinded radiologists will interpret images and provide an overall assessment of risk of malignancy to each kidney using the Bosniak criteria for each kidney lesion present. The Bosniak criteria places cystic lesions into one of 5 categories (I, II, IIF, III and IV) based on lesion characteristics. CEUS based diagnosis will be compared to the diagnoses on routine B-mode US and contrast-enhanced MRI.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7510
      • University of North Carolina of Chapel hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

To be eligible for the present study, patients must meet the following criteria:

1. Able to provide written informed consent
2. Willing to comply with protocol requirements
3. At least 16 years of age
4. Carry a diagnosis of VHL and able to undergo routine clinical screening tests for RCC

Exclusion Criteria:

1. Critically ill or medically unstable or in an intensive care setting and whose critical course during the observation period would be unpredictable
2. Known hypersensitivity to sulfur hexafluoride or to any component of perflutren lipid (Definity®) or sulfur hexafluoride (Lumason®)
3. Right to left shunt, severe pulmonary hypertension (Pulmonary artery pressure >90mmHg), or adult respiratory distress syndrome

4. Active cardiac disease including any of the following:

   A. Severe congestive heart failure (class IV in accordance with the classification of the New York Heart Association) B.Unstable angina. C.Symptomatic arrhythmia (i.e. tachycardia, bradycardia, supraventricular tachycardia, ventricular fibrillation, ventricular tachycardia, atrial flutter or fibrillation).

   D.Myocardial infarction within 14 days prior to the date of proposed microbubble administration.

5. Has any other medical condition or other circumstances that would significantly decrease the chances of obtaining reliable data or of achieving the study objectives such as:

   • Mental illness
   • Drug abuse
6. Female patient who is pregnant or lactating
7. Obesity that limits obtainment of acceptable images

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Perflutren Lipid Microsphere or Lumason; Patients with Von-Hippel Lindau disease will be imaged using contrast-enhanced ultrasound with either perflutren or Lumason.

Drug: Perflutren lipid microsphere; Baseline B-mode US will be performed to confirm the lesions being imaged (unless it is a subject with no lesions, then a basic B-mode US will be performed. Perflutren is a diagnostic drug that is intended to be used for contrast enhancement. The vial contains a clear, colorless, sterile, non-pyrogenic, hypertonic solution which is activated by mechanical agitation with Vialmix®.It will be dispensed in inactivated form to a study team member. The contrast agent will be activated just prior to administration (ideally to be used within 5 minutes of activation). Contrast agent Definity (or Lumason) will be activated according to package insert instructions, including use of VialMix®, the device used to activate Definity. Administration will occur IV in coordination with sonography staff trained specifically in contrast ultrasound imaging.The total imaging time is anticipated to be less than 30 minutes.; Other Names: • Definity®; • Microbubble contrast agent; Drug: Sulfur hexafluoride lipid microspheres; Baseline B-mode US will be performed to confirm the lesions being imaged (unless it is a subject with no lesions, then a basic B-mode US will be performed. Lumason will be used as a secondary contrast agent only if Definity(perflutren) is unavailable.This drug will be administered using the dosing range and administration type within the Lumason prescribing information. The contrast agent will be activated just prior to administration (ideally to be used within 5 minutes of activation). Contrast agent Definity (or Lumason) will be activated according to package insert instructions, including use of VialMix®, the device used to activate Definity. Administration will occur IV in coordination with sonography staff trained specifically in contrast ultrasound imaging.The total imaging time is anticipated to be less than 30 minutes.; Other Names: Lumason

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison in Radiologist's Lesion Evaluation: CEUS Versus B-mode Ultrasound	Each reader will evaluate kidney imaging using Contrast-Enhanced Ultrasound (CEUS) versus Brightness Mode Ultrasound (B-mode) in patients at risk for kidney lesions. A dichotomized Bosniak score was used for comparison. Dichotomized Bosniak score: 0= nonmalignant and 1=malignant or possibly malignant. Scores were averaged across all readers. Kidneys were assessed by CEUS and B-mode by three different readers.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison in Radiologist's Lesion Evaluation: CEUS Versus Clinically Performed MRI	Each reader will evaluate kidney imaging using Contrast-Enhanced Ultrasound (CEUS). Potentially malignant lesions were extracted from clinically performed magnetic resonance imaging (MRI) completed within 4 months of CEUS. Dichotomized Bosniak scores from CEUS were compared with MRI-derived malignancy scores. Dichotomized Bosniak scores: 0= nonmalignant and 1=malignant or possibly malignant. Scores were averaged across all readers.	Baseline

Collaborators and Investigators

• Sponsor: UNC Lineberger Comprehensive Cancer Center
• Collaborators: Lantheus Medical Imaging
• Investigators: Principal Investigator: Emily Chang, MD, University of North Carolina, Chapel Hill

Publications and helpful links

General Publications

• Larcher A, Rowe I, Belladelli F, Fallara G, Raggi D, Necchi A, Montorsi F, Capitanio U, Salonia A; OSR VHL Program. Von Hippel-Lindau disease-associated renal cell carcinoma: a call to action. Curr Opin Urol. 2022 Jan 1;32(1):31-39. doi: 10.1097/MOU.0000000000000950.

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2019
• Primary Completion (Actual): March 13, 2023
• Study Completion (Actual): March 13, 2023

Study Registration Dates

• First Submitted: April 5, 2019
• First Submitted That Met QC Criteria: April 8, 2019
• First Posted (Actual): April 9, 2019

Study Record Updates

• Last Update Posted (Actual): May 21, 2024
• Last Update Submitted That Met QC Criteria: May 16, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Disease Attributes; Congenital Abnormalities; Renal Insufficiency; Genetic Diseases, Inborn; Abnormalities, Multiple; Neurocutaneous Syndromes; Ciliopathies; Angiomatosis; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Neoplasms; Kidney Diseases; Renal Insufficiency, Chronic; Von Hippel-Lindau Disease
• Other Study ID Numbers: LCCC1824

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No