Contrast-Enhanced Ultrasound and Shear Wave Elastography for the Treatment of Lymphedema (CASTLE)

Contrast-enhanced Ultrasound and Shear Wave Elastography for the Treatment of Lymphedema (CASTLE) Study

The purpose of this research is to determine the preferred microbubble agent (Lumason®, Optison®, and Definity®) for lymphatic channel visualization by ultrasound. This research will also evaluate the utility of preoperative high-frequency B-mode ultrasound with contrast-enhanced ultrasound for presurgical planning, and ultrasound shear wave elastography for assessing treatment response at 6-month follow up.

Study Overview

• Status: Completed
• Conditions: Lymphedema Arm
• Intervention / Treatment: Drug: Lumason; Drug: Optison; Drug: Definity

Detailed Description

Part 1 - Evaluate the uptake of microbubble agent (Lumason®, Optison®, and Definity®) for lymphatic visualization by ultrasound.

Part 2 - Combine preoperative high-frequency B-mode ultrasound with contrast-enhanced ultrasound to identify patent lymphatic channels for lymphaticovenous anastomosis presurgical planning. Evaluate the utility of ultrasound shear wave elastography for assessing treatment response at 6-month follow up.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Unilateral lymphedema in the upper extremity (ISL stage 2 or 3) secondary to breast cancer or breast cancer treatment.
• Patient qualifies for LVA surgery as determined by the plastic surgeons performing the surgery (Dr. Bill Tran or Dr. Vahe Fahradyan), and the patient consents to surgery.
• Patient must be able to come to the 6-month clinical follow-up appointment (Part 2 only).
• Patients must be able to understand the study procedures and comply with them for the entire length of the study.
• No contraception is necessary or required.

Exclusion Criteria:

• Pregnant or nursing women.
• Known or suspected hypersensitivity to microbubble contrast agent, perflutren, blood products, albumin, polyethylene glycol (PEG), or egg.31.
• Known or suspected cardiac shunts.
• Prior lymphedema surgery in the upper extremity.
• Tattoo or scar on either upper extremity.
• Current drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
• Inability or unwillingness of individual or legal guardian/representative to give written informed consent..
• Current or past participation within a specified timeframe in another clinical trial, as warranted by the administration of this intervention.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Microbubble contrast agent Lumason; While subjects are undergoing standard of operation for arm with lymphedema, the healthy arm will receive intradermal injection of microbubbles and imaged immediately by ultrasound.	Drug: Lumason; Ultrasound microbubble contrast agent intradermal 0.2-0.3 cc of microbubble suspension per injection, 10-12 total injections per upper extremity; Other Names: sulfur hexafluoride lipid-type A microspheres
Other: Microbubble contrast agent Optison; While subjects are undergoing standard of operation for arm with lymphedema, the healthy arm will receive intradermal injection of microbubbles and imaged immediately by ultrasound.	Drug: Optison; Ultrasound microbubble contrast agent intradermal 0.2-0.3 cc of microbubble suspension per injection, 10-12 total injections per upper extremity; Other Names: perflutren protein-type A microspheres
Other: Microbubble contrast agent Definity; While subjects are undergoing standard of operation for arm with lymphedema, the healthy arm will receive intradermal injection of microbubbles and imaged immediately by ultrasound.	Drug: Definity; Ultrasound microbubble contrast agent intradermal 0.2-0.3 cc of microbubble suspension per injection, 10-12 total injections per upper extremity; Other Names: perflutren lipid microsphere

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lymphatic vessel visualization	The time from injection to lymphatic visualization, the duration of contrast visualization, and the longest length of lymphatic channel visualized for each injection site will be determined	5 minutes after injection
High-frequency ultrasound and shear-wave elastography	Identify any patent lymphatic channels on CEUS or high-frequency ultrasound that were not detected by the reference standard ICG lymphography. We will additionally measure dermal thickness on B-mode ultrasound and perform SWE at levels comparable to the lymphedema grading metrics routinely collected at surgical visits.	1.5 hours for intraoperative CEUS and out-patient SWE both at baseline and 6-month follow-up

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Christine Lee, MD, PhD, Mayo Clinic

Publications and helpful links

Helpful Links

• Lymphatic Mapping with Contrast-Enhanced Ultrasound (manuscript)

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2022
• Primary Completion (Actual): June 30, 2024
• Study Completion (Actual): June 30, 2024

Study Registration Dates

• First Submitted: November 4, 2022
• First Submitted That Met QC Criteria: November 4, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): August 21, 2024
• Last Update Submitted That Met QC Criteria: August 19, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Lymphaticovenous anastomosis surgery
• Additional Relevant MeSH Terms: Lymphatic Diseases; Lymphedema
• Other Study ID Numbers: 22-006006

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