Proof-of-concept Study of LymphMonitor 1.0 to Assess the Lymphatic Vessel Function

Lymphedema Clinical Trial

Official title:

Proof-of-concept Interventional Study to Evaluate the Feasibility of the New Method, LymphMonitor 1.0, to Assess Lymphatic Function, Consisting of Indocyanine Green-based Lymphatic Specific Tracer. and a Custom Fluorescence Measuring Investigational Device LymphMeter 1.0.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04393168
• Other study ID #: POCLymphMonitor 1.0
• Secondary ID: 2019-01823
• Status: Completed
• Phase: Phase 1
• Start date: May 22, 2020
• Est. completion date: June 26, 2020

Study information

• Verified date: July 2020
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Lymphedema is the consequence of injured lymphatic system and is characterized by chronic, often disabling swelling of am affected body part, often arm or leg. In the western world secondary lymphedema arises most commonly after removal lymph nodes in an operation as a part of cancer treatment (for example from the armpits or the groin region), however it may also develop as a result of radiation, any other operation, infection or injury that destroys a part of lymphatic system. The disease often develops even years after the event. While there is no cure for lymphedema at present, early detection would ensure timely physiotherapy and application of compression garments that significantly slow down or stop the progression of the disease. However, presently used methods of that are used for diagnosis and evaluating the stage of the disease, are either invasive and expensive or inaccurate and can only be performed at specialized medical centres.

Therefore, we developed a simple, affordable and accurate technology, LymphMonitor 1.0 that can allow for testing how efficiently the lymphatic system is functioning. The test can be performed at the local medical centre or potentially even at home.

In this study, we investigate whether LymphMonitor 1.0 technology can distinguish between a healthy and a diseased lymphatic system (in lymphedema). This method may allow early diagnosis of lymphedema so that the development of the disease can be detected and prevented early enough. By participating in the study the lymphedema patients are making an important contribution to increasing the quality of life of lymphedema patients. In LymphMonitor 1.0 method method, a solution of a safe fluorescent dye, indocyanine green, is injected painlessly using tiny microneedles, MicronJet600TM, directly into the skin of the arm or leg. After injection, this dye is removed from the skin only through the lymphatic vessels. The intensity of the fluorescence signal corresponds to the amount of dye left in the skin. The decrease in the fluorescence signal after the injection is measured on the surface on the skin using a new device, LymphMeter 1.0. The faster the dye (and that fluorescence signal) disappears from the surface of the skin, the better the lymphatic system works. Therefore in the arm or leg affected by lymphedema the fluorescence signal will decrease much slower compared to the healthy one.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: June 26, 2020
• Est. primary completion date: June 26, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria:

• informed consent as documented by signature

• females and males 18 - 75 years old,

• established (stage 2 or higher) unilateral secondary arm or leg lymphedema resulting from lymphadectonomy, radiation or any other surgical treatment, infection or injury.

• good general health status.

Exclusion criteria:

• critical illness (active cancer, renal failure, hepatic dysfunction)

• active infection

• blood vascular malformations or diseases

• scleroderma

• primary lymphedema

• patients who underwent any surgical procedures for treatment of lymphedema (e.g. lymphovenous anastomosis, liposuction, lymph node transfer).

• contraindications to use ICG (VERDYE), i.e.

• patients with hypersensitivity to ICG or to sodium iodide

• patients with hypersensitivity to iodine,

• patients with hyper-thyroidism, patients with autonomic thyroid adenomas

• patients in which the injection of VERDYE was poorly tolerated in the past it must not be used again, since severe anaphylactic reactions might occur.

• hypersensitivity to albumin or its excipients

• women, who are pregnant (pregnancy test will be performed in case of women who did not undergo menopause),

• women who are breast feeding ,

• enrolment of the investigator, his/her family members, employees and other dependent persons,

• known or suspected non-compliance, drug or alcohol abuse,

• inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,

• participation in another study with investigational drug within the 30 days preceding and during the present study,

• previous enrolment into the current study.

Related Conditions & MeSH terms

• Lymphedema
• Secondary Lymphedema

Intervention

Combination Product:
• Lymphatic clearance measurement
The indocyanine green in 5% human albumin solution (tracer) (50 µL) will be injected intradermally in both forearms or both lower legs using MicronJet600 microneedles paying attention to the contralateral symmetry of the injections. The signal at the injection sites will be measured over time using a hand-held portable device LymphMeter 1.0 for the total duration of 3 h. In the first hour, the signal will be measured every 15 minutes followed by measurements every half an hour. Immediately after injection (t=0 h), 1.5 h and 3 h after injection the skin area occupied by the tracer will be measured using a standard near-infrared camera, Fluobeam. The dermal reaction at the injection site will be assessed by observations for presence of redness/erythema and measuring its extent according to the needs. The patient will be constantly observed for the signs of allergic reactions, skin irritations or intolerances.

Locations

Country	Name	City	State
Switzerland	University Hostpial Zurich	Zurich

Sponsors (5)

Lead Sponsor	Collaborator
Nicole Lindenblatt	Clinical Trials Center of the University Hospital Zurich, NanoPass Technologies Ltd, Swiss Federal Institute of Technology, Zurich University of Applied Sciences

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety outcomes	Specific safety outcomes in this study will consist of any signs of potential allergic reactions and irritation of injection sites or any other intolerances	3 hours
Other	Safety outcomes	Any adverse effects (AEs) and serious adverse effects (SAEs) (expected and unexpected will be recorded	Through the study completion, an average of 5 hours
Primary	Areas under the normalized clearance curves (AUCs)	Areas under the normalized clearance curves (AUCs) in healthy and lymphedema limbs measured over 3 hours after injection. To obtain the clearance curve, the fluorescence intensity values at the injection sites in healthy and lymphedema extremities at pre-determined timepoints	Fluorescence values measured immediately after injection and 1 hour, 1.5 hours, 2 hours, 2.5 hours and 3 hours after injection.
Secondary	other clearance parameters: clearance constant (k) and half-life of clearance (t1/2); (healthy versus diseased).		Fluorescence values measured immediately after injection and 1 hour, 1.5 hours, 2 hours, 2.5 hours and 3 hours after injection.
Secondary	Correlation/no correlation of clearance parameters with the extent of the swelling (limb volume) in lymphedema patients.		3 hours
Secondary	dimensions of the injected dye depot measured by FluoBeam	Images of the injection site over time will be recorded using Fluobeam at different and analysed.	Dimensions will be measured immediately after injection and 1.5 hours and 3 hours after injection.