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

Diabetic Foot Ulcer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05274295
• Other study ID #: SZTE-CCS-DLU-01
• Status: Recruiting
• Phase: N/A
• Start date: February 28, 2022
• Est. completion date: April 30, 2022

Study information

• Verified date: March 2022
• Source: Szeged University
• Contact: Balázs Bende
• Phone: +36-62-545-277
• Email: bende.balazs[@]szte.hu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the efficacy and safety of Cytori Celution System in Hungarian patients with diabetic leg ulcers.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5
• Est. completion date: April 30, 2022
• Est. primary completion date: April 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Written informed consent

2. Males or females age = 18

3. 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

4. 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

5. Patients diagnosed with diabetes mellitus

6. Able and willing to work with the doctor, adhere to therapeutic prescriptions and appear on prescribed examinations

7. 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

8. Females of childbearing potential must have a negative pregnancy test at the Screen Visit

9. 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:

1. More than 20% change in surface area of target ulcer between screening and renrollment visit.

2. There is bone involvement in case of ulcer

3. Patient with a history of bleeding disorder

4. Therapy for anticoagulation

5. Patient receiving corticosteroids, immunosuppressive or cytotoxic agents, and all systemic agents that can affect wound repair

6. Patient with any treatment that might interfere with the assessment of the study treatment

7. Pregnant or likely to become pregnant or lactating women

8. Participation in any type of clinical investigation concurrently or in the last 6 months

9. Positive for HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) and syphilis (results within 1 month are acceptable)

10. Any concurrent disease or condition that, in the opinion of the investigator, would make the patient unsuitable for the participation in the study.

11. 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)

12. Patient currently undergoing dialysis for renal insufficiency (serum creatinine =2 mg/dL)

13. In the opinion of treating physician, patient not expected to survive beyond 30 days

14. Subjects with psychiatric conditions that are anticipated to result in protocol noncompliance

15. Uncontrolled chronic disease

16. Patient with history of severe alcohol or drug abuse

17. Lack of patient's cooperation

18. 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.

19. Systemic treatments with a possible effect on ulcers within 4 weeks prior to enrollment with the following exceptions:

1. Ustekinumab (within 16 weeks prior to enrollment)

2. Adalimum, infliximab, alefacept (within 8 weeks prior to enrollment)

Related Conditions & MeSH terms

• Diabetic Foot
• Diabetic Foot Ulcer
• Foot Ulcer
• Leg Ulcer
• Mesenchymal Stem Cells
• Ulcer

Intervention

Device:
• Diabetic leg ulcer treatment with adipous SVF
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.

Locations

Country	Name	City	State
Hungary	University of Szeged Department of Dermatology and Allergology	Szeged

Sponsors (1)

Lead Sponsor	Collaborator
Szeged University

Country where clinical trial is conducted

Hungary, 

References & Publications (9)

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop Dj, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315-7. — View Citation

Galipeau J, Krampera M, Barrett J, Dazzi F, Deans RJ, DeBruijn J, Dominici M, Fibbe WE, Gee AP, Gimble JM, Hematti P, Koh MB, LeBlanc K, Martin I, McNiece IK, Mendicino M, Oh S, Ortiz L, Phinney DG, Planat V, Shi Y, Stroncek DF, Viswanathan S, Weiss DJ, Sensebe L. International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials. Cytotherapy. 2016 Feb;18(2):151-9. doi: 10.1016/j.jcyt.2015.11.008. Epub 2015 Dec 23. — View Citation

Horwitz EM, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini FC, Deans RJ, Krause DS, Keating A; International Society for Cellular Therapy. Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy. 2005;7(5):393-5. — View Citation

Le Blanc K, Ringdén O. Immunomodulation by mesenchymal stem cells and clinical experience. J Intern Med. 2007 Nov;262(5):509-25. Review. — View Citation

Meng X, Sun B, Xue M, Xu P, Hu F, Xiao Z. Comparative analysis of microRNA expression in human mesenchymal stem cells from umbilical cord and cord blood. Genomics. 2016 Apr;107(4):124-31. doi: 10.1016/j.ygeno.2016.02.006. Epub 2016 Feb 26. — View Citation

Schwartz RE, Reyes M, Koodie L, Jiang Y, Blackstad M, Lund T, Lenvik T, Johnson S, Hu WS, Verfaillie CM. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest. 2002 May;109(10):1291-302. — View Citation

Tang Y, Yasuhara T, Hara K, Matsukawa N, Maki M, Yu G, Xu L, Hess DC, Borlongan CV. Transplantation of bone marrow-derived stem cells: a promising therapy for stroke. Cell Transplant. 2007;16(2):159-69. Review. — View Citation

Volz AC, Huber B, Kluger PJ. Adipose-derived stem cell differentiation as a basic tool for vascularized adipose tissue engineering. Differentiation. 2016 Jul-Aug;92(1-2):52-64. doi: 10.1016/j.diff.2016.02.003. Epub 2016 Mar 11. Review. — View Citation

Zachar V, Rasmussen JG, Fink T. Isolation and growth of adipose tissue-derived stem cells. Methods Mol Biol. 2011;698:37-49. doi: 10.1007/978-1-60761-999-4_4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction rate of the wound size	The treatment response will be calculated from wound size before and after treatment.	28 days
Secondary	Wound closure at Day 28	Percentage of patients achieving 50% wound closure at Day 28	28 days
Secondary	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
Secondary	Improvement Wound pain	Improvement Wound pain visual analogue scale (VAS)	28 days