A Dose-Image Optimization Trial Evaluating Mannitol and Voluven as Adjuncts for Indocyanine Green (ICGMV)

Advanced Research on ICG Fluorescence Imaging-Guided Surgery Technique Using Mannitol and Voluven as Adjuncts

The goal of this clinical trial is to exploring the use of Mannitol 20% as a solvent to prepare ICG solution, combining with Voluven, forming a hybrid small-large molecular weight solvent for protecting ICG in monomer form and stimulating lymphatic uptake simultaneously in early breast cancer patients who is indicated to undergo sentinel lymph node biopsy. The main question it aims to answer is:

• Will adding Mannitol with Voluven as ICG solvent improve the fluorescence signal of the lymph nodes, comparing with using pure Voluven?
• Which proportion of Mannitol-Voluven delivers the best image quality when used as solvent of ICG?

Researchers will compare the following arms with different solvent (all arms' final ICG concentration are 0.25mg/mL):

• Pure Voluven
• Mannitol:Voluven = 1:10
• Mannitol:Voluven = 1:8
• Mannitol:Voluven = 1:6
• Mannitol:Voluven = 1:4 to see if increased Mannitol:Voluven ratio as ICG solvent translates to better fluorescence image quality.

Participants will be invited in a group of 3, and be blindly assigned to each concentration group sequentially. Participants will undergo ICG fluorescence guided sentinel lymph node biopsy with the assigned solution formula. The endpoints included number of lymph nodes obtained, fluorescence signal-to-background ratio of the lymph nodes, lymphatic uptake rate, lymphatic drainage speed, detection method, lymph node pathology, and any intra- or post-operative complications.

Study Overview

• Status: Enrolling by invitation
• Conditions: Breast Cancer Early Stage Breast Cancer (Stage 1-3)
• Intervention / Treatment: Procedure: Voluven-assisted Indocyanine green fluorescence guided sentinel lymph node biopsy for breast cancer; Drug: Mannitol (20%)

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Hsinchu County, Taiwan, 302
    • National Taiwan University Hospital Hsinchu branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult females aged 20 to 70 years old.
• Pathologically confirmed invasive breast cancer patients who are eligible for sentinel lymph node biopsy.

Exclusion Criteria:

• History of allergy to iodine, ICG, blue dye, Voluven, or Mannitol.
• History of hyperthyroidism, thyroid cancer, etc.
• Current pregnancy, lactation, or breast infection.
• Individuals with impaired mental capacity or belonging to vulnerable populations.
• Patients who have undergone neoadjuvant chemotherapy prior to surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pure Voluven; The solution is prepared using Voluven as solvent, forming a 0.25 mg/mL ICG:Voluven solution.	Procedure: Voluven-assisted Indocyanine green fluorescence guided sentinel lymph node biopsy for breast cancer; The procedure includes: (1) preparation of specific formula of ICG:Voluven solution (2) injection of ICG solution at subarelar area or peri-tumoral area (3) observation of fluorescent lymphatic drainage and retrieval of sentinel lymph nodes
Active Comparator: 1:10; The solution is prepared using Mannitol(20%):Voluven=1:10 as solvent, forming a 0.25 mg/mL ICG:Solvent solution.	Procedure: Voluven-assisted Indocyanine green fluorescence guided sentinel lymph node biopsy for breast cancer; The procedure includes: (1) preparation of specific formula of ICG:Voluven solution (2) injection of ICG solution at subarelar area or peri-tumoral area (3) observation of fluorescent lymphatic drainage and retrieval of sentinel lymph nodes; Drug: Mannitol (20%); Adding Mannitol into Voluven and used as solvent of ICG
Active Comparator: 1:8; The solution is prepared using Mannitol(20%):Voluven=1:8 as solvent, forming a 0.25 mg/mL ICG:Solvent solution.	Procedure: Voluven-assisted Indocyanine green fluorescence guided sentinel lymph node biopsy for breast cancer; The procedure includes: (1) preparation of specific formula of ICG:Voluven solution (2) injection of ICG solution at subarelar area or peri-tumoral area (3) observation of fluorescent lymphatic drainage and retrieval of sentinel lymph nodes; Drug: Mannitol (20%); Adding Mannitol into Voluven and used as solvent of ICG
Active Comparator: 1:6; The solution is prepared using Mannitol(20%):Voluven=1:6 as solvent, forming a 0.25 mg/mL ICG:Solvent solution.	Procedure: Voluven-assisted Indocyanine green fluorescence guided sentinel lymph node biopsy for breast cancer; The procedure includes: (1) preparation of specific formula of ICG:Voluven solution (2) injection of ICG solution at subarelar area or peri-tumoral area (3) observation of fluorescent lymphatic drainage and retrieval of sentinel lymph nodes; Drug: Mannitol (20%); Adding Mannitol into Voluven and used as solvent of ICG
Active Comparator: 1:4; The solution is prepared using Mannitol(20%):Voluven=1:4 as solvent, forming a 0.25 mg/mL ICG:Solvent solution.	Procedure: Voluven-assisted Indocyanine green fluorescence guided sentinel lymph node biopsy for breast cancer; The procedure includes: (1) preparation of specific formula of ICG:Voluven solution (2) injection of ICG solution at subarelar area or peri-tumoral area (3) observation of fluorescent lymphatic drainage and retrieval of sentinel lymph nodes; Drug: Mannitol (20%); Adding Mannitol into Voluven and used as solvent of ICG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of sentinel lymph nodes	The number of the retrieved sentinel lymph nodes	From the procedure day to the follow-up clinic visit day (average 10 days)
Fluorescence signal-to-background ratio of the lymph nodes		From the procedure day to the follow-up clinic visit day (average 10 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lymphatic uptake rate	The time from injection to the development of fluorescent subcutaneous lymphatics	From the procedure day to the follow-up clinic visit day (average 10 days)
Lymphatic drainage speed	The time from the initiation of visible fluorescent subcutaneous lymphatics to that reaches the axilla	From the procedure day to the follow-up clinic visit day (average 10 days)
Detection method	The method of the sentinel lymph node being detected. (Could be radioisotope, blye dye, ICG fluorescence, or combination of multiple methods)	From the procedure day to the follow-up clinic visit day (average 10 days)
Lymph node pathology	The positivity of sentinel lymph node metastasis in the pathology report.	From the procedure day to the follow-up clinic visit day (average 10 days)

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: National Taiwan University Hospital Hsin-Chu Branch; National Yang Ming Chiao Tung University
• Investigators: Study Chair: Yung Chun Hsieh, M.D., MMSC, National Taiwan University Hospital Hsinchu branch

Publications and helpful links

General Publications

• Hsieh YC, Guo KW, Wang MW, Su SP, Syu YH, Huang CS, Chan YH. A Novel Injection Protocol Using Voluven(R)-Assisted Indocyanine Green with Improved Near-Infrared Fluorescence Guidance in Breast Cancer Sentinel Lymph Node Mapping-A Translational Study. Ann Surg Oncol. 2023 Dec;30(13):8419-8427. doi: 10.1245/s10434-023-14129-4. Epub 2023 Aug 21.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: December 29, 2024
• First Submitted That Met QC Criteria: January 6, 2025
• First Posted (Actual): January 10, 2025

Study Record Updates

• Last Update Posted (Actual): April 16, 2025
• Last Update Submitted That Met QC Criteria: April 15, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: mannitol; breast cancer; indocyanine green; sentinel lymph node biopsy; fluorescence-guided surgery; near-infrared fluorescence; 6-hydroxyethyl starch
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Diuretics; Natriuretic Agents; Diuretics, Osmotic; Mannitol
• Other Study ID Numbers: 202409024MIND; 114-BIH052 (Other Grant/Funding Number: National Taiwan University Hospital Hsinchu Branch)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No