Cold Plasma Therapy for Acceleration of Wound Healing in Diabetic Foot

Study Overview
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Brief Summary
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Diabetic foot is a common complication of diabetes mellitus and requires specialized treatment. Wounds are characterized by persistent infection and chronic inflammatory processes, impeding well directed matrix remodelling and wound closure. Cold plasma applications have demonstrated beneficial effects on wound healing in several case reports. The investigator-initiated Kaltplasma Wund (KPW)-Trial was performed to prove beneficial effects of cold plasma in wound healing in a prospective, placebo-controlled, randomized bi-center study.

Detailed Description
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Diabetic foot (DF) is a major complication in patients with diabetes leading to increased risk of hospitalization, lower limb amputation, and death, as well as a significant decrease in quality of life. During lifetime the risk for developing DF is assumed to be 25%; with 30% of DF resulting in lower limb amputation. If compared to general population people with diabetes have a 20-fold higher risk for amputation. Diabetes mellitus is the leading cause of lower limb amputation. Ulceration and impaired wound healing are commonly associated with common co-morbidities; the increased risk of infection amongst patients with diabetes is driving chronification and accounts for lack of wound healing. Non-thermal atmospheric pressure plasma has been proposed as a tool for various biological and medical applications relying on its capacity to reduce bacterial load in the wound and to initiate wound healing. Biological plasma effects are largely dependent on plasma-generated reactive species in the gas phase, which subsequently diffuse or react with proteins and lipids in cells or tissues. Thus, the objective of this placebo-controlled patient-blinded study was to show that application of cold plasma in addition to standard care treatment compared to placebo could accelerate wound healing in terms of more rapid and clinical meaningful wound surface regression. Wound closure progression and microbiological analysis were monitored time dependently to prove the effects. Patient's well-being and subjective perceptions were evaluated during treatment.

Official Title
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Cold Plasma Therapy for Acceleration of Wound Healing in Superficial, Infected Diabetic Foot

Conditions
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Diabetic Foot

Intervention / Treatment
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* Device: Argon Plasma Jet
* Device: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 or Type 2 Diabetes mellitus HbA1c ≤ 10% at least one chronic wound persisting for at least three weeks without healing tendency following standard care wound therapy (Armstrong Wagner Grade Ib or IIb) Exclusion Criteria: concomitant wound treatment with local vacuum therapy or maggot therapy dialysis use of topical active antibiotics, concomitant treatment with platelet rich fibrin, presence of critical limb ischemia defined as ankle brachial index below 0.5 or transcutaneous oxygen pressure below 15 mmHg. participation in another clinical trial women of child bearing potential without effective contraception or active breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Plasma<br>regular treatment with Argon Plasma Jet according to manufacturer's instructions, 8 times within 14 days | Device: Argon Plasma Jet<br>* Cold Plasma (CP) therapy is applied in the first week of treatment on a daily schedule, in the second week CP is applied every second day. In total, 8 applications are performed with a one day schedule variance.<br>|
| Sham Comparator: Placebo<br>Sham-treatment with Argon Plasma Jet, Plasma producing electric field switched off - no Plasma is produced, just argon gas as effluent, 8 times within 14 days | Device: Placebo<br>* Sham Cold Plasma (sham-CP) (switched off Electric field, no plasma production, just gas) therapy is applied in the first week of treatment on a daily schedule, in the second week sham-CP is applied every second day. In total, 8 applications are performed with a one day schedule variance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in wound surface area | change in wound surface area within 14 days treatment | treatment period of max 15 days | 
| change in signs of clinical infection | change in clinical signs of infections as judged by the investigator | treatment period of max 15 days | 
| change in microbial load | change in microbial count, being evaluated by microbial culture | treatment period of max 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to significant wound surface area change | time to 10% reduction of wound surface compared to treatment start | treatment period of max 15 days | 
| total wound surface change during treatment | total wound surface change compared to treatment start | treatment period of max 15 days | 
| time to change in wound infection | change in wound infection over treatment | treatment period of max 15 days | 
| changes in Quality of life (EQ5D questionnaire) | Evaluation of life quality during (EQ5D questionnaire) treatment period via questionaire | treatment period of max 15 days | 
| changes in Quality of life (SF12 questionnaire) | Evaluation of life quality during (SF12 questionnaire) treatment period via questionaire | treatment period of max 15 days | 
| treatment related side effects - formation of keloids | question to evaluate potential side effects of the therapy: formation of keloids will be answered in a yes or no fashion and reported | treatment period of max 15 days | 
| treatment related side effects - presence of skin irritation | question to evaluate potential side effects of the therapy: presence of skin irritation will be answered in a yes or no fashion and reported | treatment period of max 15 days | 
| treatment related side effects - local bleeding | question to evaluate potential side effects of the therapy: local bleeding will be answered in a yes or no fashion and reported | treatment period of max 15 days | 
| treatment related side effects - proliferative skin reaction | question to evaluate potential side effects of the therapy: proliferative skin reaction will be answered in a yes or no fashion and reported | treatment period of max 15 days |