Air Cold Atmospheric Pressure Plasma Treatment for Acceleration of Venous Ulcer Healing

Venous Leg Ulcer Clinical Trial

— PLASFRI-CUV  

Official title:

Air Cold Atmospheric Pressure Plasma Treatment for Acceleration of Venous Ulcer Healing

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05894096
• Other study ID #: PLASFRI-CUV
• Status: Recruiting
• Phase: N/A
• Start date: March 24, 2023
• Est. completion date: June 30, 2024

Study information

• Verified date: May 2023
• Source: Clinica Universidad de Navarra, Universidad de Navarra
• Contact: Bernardo Hontanilla, Ph.D.
• Phone: +34 948 255 400
• Email: bhontanill[@]unav.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this medical trial, a novel prototype of a medical device based on a Cold Atmospheric Air Plasma Jet for the treatment is clinically tested on patients with venous leg ulcers. The device is characterized by producing the first cold air plasma jet compatible with living tissues at a low heat transfer rate with a temperature on the skin surface lower than 40 ºC. It has a practical design to be used by physicians during daily practice with a special focus on unhealed ulcers.

Description:

The device to be validated in this test is an air-generating unit in a cold plasma state, a prototype of a medical device. Cold plasma-generating equipment is already available on the market and is intended for the treatment of chronic ulcers in patients. Its technology is based on the generation of a plasma jet produced with the noble gas argon. The novelty of this new plasma generator lies in the fact that its production is carried out by using atmospheric air, which implies greater efficiency and ease of use, being the first of its kind at an international level. The main mechanism of action underlying the therapeutic effect of cold atmospheric plasmas is the effect of the electric fields produced by the charged particles that make up the air in the plasma state. These fields are imperceptible to the patient, however, the effect on microcirculation in the area of application of the wound is very noticeable. The improvement in microcirculation extends for a longer time than the treatment as demonstrated by reported oxygen saturation studies using cold air plasmas DBD (Dielectric Barrier Discharge) that include clinical trials (1-4). Enhanced capillary blood flow increases local oxygen saturation and nutrient supply, thus promoting wound healing (5). In addition to the action of electric fields, there is an auxiliary decontamination mechanism generated by the emission of ultraviolet radiation, below the damage threshold for humans and excited and ionized oxygen and nitrogen molecules. This mechanism eliminates bacteria, including resistant ones, so that the regeneration capacity promoted by the main mechanism of action is enhanced (6-8).

The generator chosen for this test belongs to the Spanish company ION BIOTEC S.L. (PlasmAction Med), which has obtained an international patent (9). Its use in animals has been successfully developed in veterinary clinics and the positive results obtained in the closure of torpid ulcers using cold atmospheric plasmas have been demonstrated (10-13). The plasma jet is applied directly to the lesion presented by the patient with a power of 55% and with an intensity and duration of 60 s/cm2, by means of the regulator found at the end of an application hose. It does not use consumables or produce waste.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 68
• Est. completion date: June 30, 2024
• Est. primary completion date: March 24, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Be of legal age (18 years).

• Signed informed consent.

• Presenting at least one venous ulcer larger than 1 cm2 that has not healed in the last 3 weeks from its appearance.

• Absence of surgical indication for ulcer coverage by skin graft.

Exclusion Criteria:

• Uncontrolled diabetes mellitus (HbA1c > 8%). If during the trial the patient suffers a decompensation of diabetes, it will be considered an adverse event.

• Patient allergic to silver or any other material that will be used during the cure of the ulcer under study.

• Concomitant treatment with vacuum-assisted closure (VAC) therapy.

• Use of topical antibiotic therapy. The minimum washing time should be 48 hours.

• Presence of critical limb ischemia defined as an ankle-brachial index (ABI) below 0.5 or a transcutaneous O2 pressure (TcPO2) below 15 mmHg.

• Treatment with corticosteroids in the 14 days prior to the study or with other immunosuppressants.

• Presence of a chronic or active skin disorder that may negatively influence wound healing (such as Marfan or Ehlers-Danlos syndrome, systemic lupus erythematosus, systemic sclerosis, or psoriasis).

• Pregnancy or lactation.

• Advanced or metastatic stage cancer.

• Deficiency states.

• Dementia.

• Post radiation wounds.

• Sepsis.

Related Conditions & MeSH terms

• Leg Ulcer
• Ulcer
• Varicose Ulcer
• Venous Leg Ulcer

Intervention

Device:
• Cold Atmospheric Plasma Jet Treatment
Application of Colf Atmospheric Plasma Jet on the wound
• Alginate Patch
Application of Alginate Patches on the wound

Locations

Country	Name	City	State
Spain	Clinica Universidad de Navarra	Madrid
Spain	Clinica Universidad de Navarra	Pamplona	Navarra

Sponsors (2)

Lead Sponsor	Collaborator
Clinica Universidad de Navarra, Universidad de Navarra	Hospital General Universitario Gregorio Marañon

Country where clinical trial is conducted

Spain, 

References & Publications (15)

A. Nishijima. A New Energy Device for Skin Activation to Acute Wound Using Cold Atmospheric Pressure Plasma: A Randomized Controlled Clinical Trial. Biomed J Sci Tech Res. 2019;21(1):15494-501. DOI: 10.26717/BJSTR.2019.21.003532

Amini MR, Sheikh Hosseini M, Fatollah S, Mirpour S, Ghoranneviss M, Larijani B, Mohajeri-Tehrani MR, Khorramizadeh MR. Beneficial effects of cold atmospheric plasma on inflammatory phase of diabetic foot ulcers; a randomized clinical trial. J Diabetes Metab Disord. 2020 Jul 14;19(2):895-905. doi: 10.1007/s40200-020-00577-2. eCollection 2020 Dec. — View Citation

Brany D, Dvorska D, Halasova E, Skovierova H. Cold Atmospheric Plasma: A Powerful Tool for Modern Medicine. Int J Mol Sci. 2020 Apr 22;21(8):2932. doi: 10.3390/ijms21082932. — View Citation

Brehmer F, Haenssle HA, Daeschlein G, Ahmed R, Pfeiffer S, Gorlitz A, Simon D, Schon MP, Wandke D, Emmert S. Alleviation of chronic venous leg ulcers with a hand-held dielectric barrier discharge plasma generator (PlasmaDerm((R)) VU-2010): results of a monocentric, two-armed, open, prospective, randomized and controlled trial (NCT01415622). J Eur Acad Dermatol Venereol. 2015 Jan;29(1):148-55. doi: 10.1111/jdv.12490. Epub 2014 Mar 25. — View Citation

Chuangsuwanich A, Assadamongkol T, Boonyawan D. The Healing Effect of Low-Temperature Atmospheric-Pressure Plasma in Pressure Ulcer: A Randomized Controlled Trial. Int J Low Extrem Wounds. 2016 Dec;15(4):313-319. doi: 10.1177/1534734616665046. Epub 2016 Sep 20. — View Citation

Cooper M, Fridman G, Fridman A, Joshi SG. Biological responses of Bacillus stratosphericus to floating electrode-dielectric barrier discharge plasma treatment. J Appl Microbiol. 2010 Dec;109(6):2039-48. doi: 10.1111/j.1365-2672.2010.04834.x. — View Citation

CORTÁZAR PÉREZ OD, MEGIA MACÍAS AM. Electromedical device for blood clotting and treatment of ulcers and other skin injuries in human and animal patients. 2020.

Heuer K, Hoffmanns MA, Demir E, Baldus S, Volkmar CM, Rohle M, Fuchs PC, Awakowicz P, Suschek CV, Oplander C. The topical use of non-thermal dielectric barrier discharge (DBD): nitric oxide related effects on human skin. Nitric Oxide. 2015 Jan 30;44:52-60. doi: 10.1016/j.niox.2014.11.015. Epub 2014 Nov 27. — View Citation

Jensen JO, Schulz L, Schleusser S, Matzkeit N, Stang FH, Mailaender P, Kraemer R, Kleemann M, Deichmann H, Kisch T. The repetitive application of cold atmospheric plasma (CAP) improves microcirculation parameters in chronic wounds. Microvasc Res. 2021 Nov;138:104220. doi: 10.1016/j.mvr.2021.104220. Epub 2021 Jun 30. — View Citation

Kisch T, Helmke A, Schleusser S, Song J, Liodaki E, Stang FH, Mailaender P, Kraemer R. Improvement of cutaneous microcirculation by cold atmospheric plasma (CAP): Results of a controlled, prospective cohort study. Microvasc Res. 2016 Mar;104:55-62. doi: 10.1016/j.mvr.2015.12.002. Epub 2015 Dec 3. — View Citation

Kisch T, Schleusser S, Helmke A, Mauss KL, Wenzel ET, Hasemann B, Mailaender P, Kraemer R. The repetitive use of non-thermal dielectric barrier discharge plasma boosts cutaneous microcirculatory effects. Microvasc Res. 2016 Jul;106:8-13. doi: 10.1016/j.mvr.2016.02.008. Epub 2016 Mar 2. — View Citation

Matzkeit N, Schulz L, Schleusser S, Jensen JO, Stang FH, Mailaender P, Kramer R, Kisch T. Cold atmospheric plasma improves cutaneous microcirculation in standardized acute wounds: Results of a controlled, prospective cohort study. Microvasc Res. 2021 Nov;138:104211. doi: 10.1016/j.mvr.2021.104211. Epub 2021 Jun 16. — View Citation

MORFILL G. TREATING DEVICE FOR TREATING A BODY PART OF A PATIENT WITH A NON-THERMAL PLASMA. WO 2010/094307 Al, 2009.

Ulrich C, Kluschke F, Patzelt A, Vandersee S, Czaika VA, Richter H, Bob A, Hutten Jv, Painsi C, Huge R, Kramer A, Assadian O, Lademann J, Lange-Asschenfeldt B. Clinical use of cold atmospheric pressure argon plasma in chronic leg ulcers: A pilot study. J Wound Care. 2015 May;24(5):196, 198-200, 202-3. doi: 10.12968/jowc.2015.24.5.196. — View Citation

Ziuzina D, Boehm D, Patil S, Cullen PJ, Bourke P. Cold Plasma Inactivation of Bacterial Biofilms and Reduction of Quorum Sensing Regulated Virulence Factors. PLoS One. 2015 Sep 21;10(9):e0138209. doi: 10.1371/journal.pone.0138209. eCollection 2015. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ulcer Surface	The surface of the ulcer will be meassured by means of sofware image J2	18 weeks
Secondary	Measurement of bacterial burden	Bacteriological cultures will be taken before and after of the treated group at 0, 5 and 10 weeks. Control groups at º, 5 and 10 weeks.	18 weeks