Clinical trial NCT04205942: Cold Plasma Therapy for Acceleration of Wound Healing in Diabetic Foot
Official title: Cold Plasma Therapy for Acceleration of Wound Healing in Superficial, Infected Diabetic Foot
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Diabetic Foot
Lead sponsor: Ruhr University of Bochum
Sponsor class: OTHER
First posted: 2019-12-20
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: change in wound surface area
timeFrame: treatment period of max 15 days
measure: change in signs of clinical infection
timeFrame: treatment period of max 15 days
measure: change in microbial load
timeFrame: treatment period of max 15 days
Secondary outcomes:
measure: time to significant wound surface area change
timeFrame: treatment period of max 15 days
measure: total wound surface change during treatment
timeFrame: treatment period of max 15 days
measure: time to change in wound infection
timeFrame: treatment period of max 15 days
measure: changes in Quality of life (EQ5D questionnaire)
timeFrame: treatment period of max 15 days
measure: changes in Quality of life (SF12 questionnaire)
timeFrame: treatment period of max 15 days
measure: treatment related side effects - formation of keloids
timeFrame: treatment period of max 15 days
measure: treatment related side effects - presence of skin irritation
timeFrame: treatment period of max 15 days
measure: treatment related side effects - local bleeding
timeFrame: treatment period of max 15 days
measure: treatment related side effects - proliferative skin reaction
timeFrame: treatment period of max 15 days
Other outcomes:
measure: treatment related side effects - formation of keloids
timeFrame: within 5 years after start of treatment (at 1, 2 and 5 years after start of treatment)
measure: treatment related side effects - presence of skin irritation
timeFrame: within 5 years after start of treatment (at 1, 2 and 5 years after start of treatment)
measure: treatment related side effects - local bleeding
timeFrame: within 5 years after start of treatment (at 1, 2 and 5 years after start of treatment)
measure: treatment related side effects - proliferative skin reaction
timeFrame: within 5 years after start of treatment (at 1, 2 and 5 years after start of treatment)
Locations:
Study officials:
affiliation: Herz- und Diabeteszentrum NRW, Ruhr-Universität Bochum
name: Diethelm Tschoepe, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hiller J, Stratmann B, Timm J, Costea TC, Tschoepe D. Enhanced growth factor expression in chronic diabetic wounds treated by cold atmospheric plasma. Diabet Med. 2022 Jun;39(6):e14787. doi: 10.1111/dme.14787. Epub 2022 Jan 21.
citation: Stratmann B, Costea TC, Nolte C, Hiller J, Schmidt J, Reindel J, Masur K, Motz W, Timm J, Kerner W, Tschoepe D. Effect of Cold Atmospheric Plasma Therapy vs Standard Therapy Placebo on Wound Healing in Patients With Diabetic Foot Ulcers: A Randomized Clinical Trial. JAMA Netw Open. 2020 Jul 1;3(7):e2010411. doi: 10.1001/jamanetworkopen.2020.10411.