Open Label Single Arm Proof of Concept Trial to Evaluate the Efficacy and Safety of Cytori Celution System in Diabetic Leg Ulcers

Study Overview
=================
Brief Summary
-----------------
To evaluate the efficacy and safety of Cytori Celution System in Hungarian patients with diabetic leg ulcers.

Detailed Description
-----------------
This motive trial can help to establish rutine application of this internationaly widely used device at University of Szeged. The primary outcome is the reduction rate of the wound size. The treatment response will be calculated from wound size before and after treatment. Any AEs related to the study devide will be monitored.

Official Title
-----------------
Open Label Single Arm Proof of Concept Trial to Evaluate the Efficacy and Safety of Cytori Celution System in Diabetic Leg Ulcers

Conditions
-----------------
Diabetic Foot Ulcer, Leg Ulcer, Autologous Adipose Stromal Vascular Fraction, Mesenchymal Stem Cells, Adipose-Derived Mesenchymal Stem Cells

Intervention / Treatment
-----------------
* Device: Diabetic leg ulcer treatment with adipous SVF


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent Males or females age ≥ 18 At least one diabetic leg ulcer with the following condition 3.1. Ulcer is present beyond 2 months 3.2. Conservative treatment not leading to improvement 3.3. Wound size between ≥5 and ≤100 cm2 Ability to safely undergo tissue harvest that is anticipated to yield >100mL of adipose tissue at a site that is free from infection and injury Patients diagnosed with diabetes mellitus Able and willing to work with the doctor, adhere to therapeutic prescriptions and appear on prescribed examinations Normal or clinically not significant abnormal values based on investigator judgement on white blood cell count (WBC), C-reactive protein (CRP), Platelets, international normalized ratiod (INR), partial thromboplastin time (APTT), haemoglobin (Hgb), Renal and Liver function Females of childbearing potential must have a negative pregnancy test at the Screen Visit Females of childbearing potential must agree to use a highly effective method of birth control during the study. A highly effective method of birth control is defined as one which has a proven low failure rate of less than 1% Exclusion Criteria: More than 20% change in surface area of target ulcer between screening and renrollment visit. There is bone involvement in case of ulcer Patient with a history of bleeding disorder Therapy for anticoagulation Patient receiving corticosteroids, immunosuppressive or cytotoxic agents, and all systemic agents that can affect wound repair Patient with any treatment that might interfere with the assessment of the study treatment Pregnant or likely to become pregnant or lactating women Participation in any type of clinical investigation concurrently or in the last 6 months Positive for HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) and syphilis (results within 1 month are acceptable) Any concurrent disease or condition that, in the opinion of the investigator, would make the patient unsuitable for the participation in the study. Active cancer during chemotherapy or radiotherapy, or recent cancer, if the remission had place less than 5 years before joining the study (except basal cell skin cancer) Patient currently undergoing dialysis for renal insufficiency (serum creatinine ≥2 mg/dL) In the opinion of treating physician, patient not expected to survive beyond 30 days Subjects with psychiatric conditions that are anticipated to result in protocol noncompliance Uncontrolled chronic disease Patient with history of severe alcohol or drug abuse Lack of patient's cooperation Use with blood thinners within 8 weeks of enrollment, patients treated with Acetylsalicil Acid (ASA) are allowed to be enrolled. For these patients ASA therapy has to be swiched to Low Molecular Weight Heparin (LMWH) at screening (after cardiology consultation) for one week. LMWH has to be skipped on enrollment visit and ASA has to be re-started as soon as possible after lipoaspiration performed. Systemic treatments with a possible effect on ulcers within 4 weeks prior to enrollment with the following exceptions: Ustekinumab (within 16 weeks prior to enrollment) Adalimum, infliximab, alefacept (within 8 weeks prior to enrollment)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cytori Celution System in Chronic Non-Healing diabetic Leg Ulcers<br>On the screening visit, the study physician will assign one eligible ulcer, as the target ulcer. Target ulcer will be treated and followed up during the whole study period. After liposuction investigational device will be applied on the target ulcer. After completion of Day1 visit all subjects enter the observation period and will come back to 3 on-site visits on day 7 day 14 and day 28 | Device: Diabetic leg ulcer treatment with adipous SVF<br>* The Celution® System isolates approximately maximum 30 million SVF cells per 100 mL of adipose tissue to be processed. Approximately 1-3 million cells per injection (total 8-30) will be administered locally, in the target ulcer.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction rate of the wound size | The treatment response will be calculated from wound size before and after treatment. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Wound closure at Day 28 | Percentage of patients achieving 50% wound closure at Day 28 | 28 days | 
| Improvement of Quality of Life (QoL) - EQ-5D-5L | The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. | 25 days | 
| Improvement Wound pain | Improvement Wound pain visual analogue scale (VAS) | 28 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cytori Celution System