Effect Of Resistive Capactive Electrical Transfer Therapy In Difficult-to-heal Wounds

Effect Of Resistive Capactive Electrical Transfer Therapy On Wound Healing And Biomarker Expression In Difficult-to-heal Wounds

Difficult-to-heal wounds present imbalances in cytokine production, increases in MMP expression, high levels of apoptosis, and decreases in the proliferation of cells such as fibroblasts and keratinocytes, which are involved in tissue regeneration. CRET therapy (capacitive resistive electrical transfer therapy) has been shown to generate granulation tissue in in vitro assays. In addition, available clinical case reports and preliminary clinical trial results indicate that CRET can promote the regeneration of acute wounds and DHW (difficult-to-heal wounds).

Study Overview

• Status: Not yet recruiting
• Conditions: Difficult-to-heal Wounds
• Intervention / Treatment: Device: OKTO; Device: Standard clinical procedures

Detailed Description

Difficult-to-heal wounds present imbalances in cytokine production, increases in MMP expression, high levels of apoptosis, and decreases in the proliferation of cells such as fibroblasts and keratinocytes, which are involved in tissue regeneration. CRET therapy has been shown to be able to generate granulation tissue in in vitro assays. In addition, available clinical case reports and preliminary clinical trial results indicate that CRET can promote acute wound regeneration and CDH.

The working hypothesis is that CRET treatment promotes the healing of CDH through its action in regulating inflammatory and regenerative processes in skin tissue. This non-invasive, cost-effective treatment, devoid of identified adverse effects, and not studied in depth so far in patients with CDH, can thus be placed in the treatment algorithms of CDH with the correct selection of candidate patients.

• Study Type: Interventional
• Enrollment (Estimated): 137
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years of age or older
• Agree to participate in the study and sign the informed consent form.
• Inpatients or outpatients who can be followed by the research team for the duration of the study
• Ulcers with a surface area of no less than 0.5 cm2 and of at least 4 weeks' duration (CDH), located on the lower limbs in the case of ulcers of venous etiology or on the foot, in the case of diabetic foot ulcers.
• For patients with ulcers of venous etiology: ulcers of venous etiology stage 2, 3 4 with diagnosis of chronic venous insufficiency with open wound CEAP IVC C6 according to CEAP classification (38).

• For patients with diabetic foot ulcers presenting:

  • Type 1 and type 2 diabetics with a glycated hemoglobin (HbA1c ≤10% (in a test no longer than 3 months).
  • Patients with UPD without PAD or with associated mild or moderate stage PAD (39) according to the criteria of the intersociety consensus for the treatment of peripheral arterial disease (TASC II).
  • UPD Grade 1A, 1C, 2A, 2C according to the Texas classification (40).
  • Patients who have required previous surgical debridement and 4 weeks have elapsed since such debridement.

• Comorbidity is defined as the presence of at least one of the following criteria:

  • Smoking more than 10 cigarettes per day in the last 6 months.
  • Immunosuppression: systemic treatment with high-dose corticosteroids in the previous 3 months, severe active infection in the previous month, presence of systemic or organ-specific autoimmune disease.
  • Renal failure with creatinine > 2 mg/dl.
  • Respiratory failure with pO2< 90 mm Hg
  • Cardiac failure, grade II or higher
  • Anemia or nutritional deficit
  • Endocrine disruption under medical treatment
  • Neuropathy in the affected area or neurological disease.
  • Connective tissue diseases
  • Mobility impairment
  • Presence of microvascular disease

Exclusion Criteria:

• Pregnancy
• Patients with contraindications for CRET treatments (electronic implants, thrombophlebitis).
• Patients with chronic or pathological wounds that required surgical intervention.
• Ulcers with active infection according to IDSA classification in soft tissues or with clinical and/or radiological signs compatible with osteomyelitis.
• Allergies to standard wound treatment.
• Patients presenting severe renal insufficiency (Glomerular filtration rate ≤30 ml/min in analysis performed in the last 3 months).
• Patient who has presented an acute ischemic event (acute myocardial infarction or stroke, in the 3 months prior to inclusion in the study).
• Patients who present an evolving neoplastic condition, treated by radiotherapy, chemotherapy, hormone therapy or immunosuppressants at the current moment.
• Patients treated for a chronic condition requiring the intake of strong systemic corticosteroids doses ≥ 40 mg prednisone).
• Critical non-revascularizable ischemia or TcPO2 < 25mmHg or a digital hallux systolic pressure < 50 mm Hg in diabetic foot ulcers.
• Patients who do not accept to use the prescribed unloading treatment in the case of diabetic foot ulcers.
• In the case of patients with ulcers of venous etiology, the presence of peripheral arterial disease in any of its stages.
• Patients who do not accept the indicated compressive bandage treatment, in the case of ulcers of venous etiology.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A-E group; Treatment with radiofrequency currents of resistive capacitive electrical transfer therapy (CRET) under hyperthermia conditions plus standard clinical treatments, in patients with ulcers of venous etiology.	Device: OKTO; Static Monopolar Capacitive Resistive Resistive Radiofrequency Equipment at 448 kHz; Device: Standard clinical procedures; standard clinical procedures
Experimental: B-E group; Treatment with radiofrequency currents of resistive capacitive electrical transfer therapy (CRET) under hyperthermia conditions plus standard clinical treatments in patients with diabetic foot ulcers.	Device: OKTO; Static Monopolar Capacitive Resistive Resistive Radiofrequency Equipment at 448 kHz; Device: Standard clinical procedures; standard clinical procedures
Experimental: A-C grouop; Treatment with radiofrequency currents of resistive capacitive electrical transfer therapy (CRET) under hyperthermia conditions plus standard clinical treatments in CDH.	Device: OKTO; Static Monopolar Capacitive Resistive Resistive Radiofrequency Equipment at 448 kHz; Device: Standard clinical procedures; standard clinical procedures
Experimental: B-C grouop; Treatment with radiofrequency currents of resistive capacitive electrical transfer therapy (CRET) under subthermal conditions plus standard clinical treatments in CDH.	Device: OKTO; Static Monopolar Capacitive Resistive Resistive Radiofrequency Equipment at 448 kHz; Device: Standard clinical procedures; standard clinical procedures
Experimental: C-C group; Standard clinical treatments established on the basis of the treatment standards of the International Working Group on the Diabetic Foot (IWGDF), in the case of diabetic foot ulcers (2, 3). For ulcers of venous etiology, the treatment standards according to the guidelines of the Spanish Association of Vascular Nursing and Wounds (Asociación Española de Enfermería Vascular y Heridas) will also be applied.	Device: Standard clinical procedures; standard clinical procedures

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wound dimensions before and after treatments in patients with HDC treated with CRET therapy plus standard treatment versus patients with HDC undergoing standard treatment alone.	Wound dimensions measurement (area, length and width) before and after treatments in patients with HDC treated with CRET therapy plus standard treatment versus patients with HDC undergoing standard treatment alone.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
General clinical evaluation:	age,; sex,; BMI; general medical history,; baseline blood work,; usual treatment	18 months
Wound evaluation:	cause,; location,; time of evolution,; photographs.	18 months
Evaluation of biomarkers in peripheral blood of patients with CDH with or without CRET treatment:	Quantification of cytokines and growth factors: IL-1α, IL-1β, TNFα, IFγ.	18 months
In primary cultures of fibroblasts isolated from biopsies of CDH patients with or without CRET treatment, assessment of typical CDH biomarkers related to:	Death: TUNEL assay; Bcl-2, Bcl-X and Caspase-3 markers.; Viability/proliferation: XTT, Ki67, p-p38 and p-ERK1/2 assays.; Adhesion: β -catenin and E-cadherin.; Extracellular matrix: α-SMA, Col I and Col III and the metalloproteinases, MMP8, MMP2 and MMP9.	18 months

Collaborators and Investigators

• Sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: June 29, 2023
• First Submitted That Met QC Criteria: July 18, 2023
• First Posted (Actual): July 20, 2023

Study Record Updates

• Last Update Posted (Actual): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries
• Other Study ID Numbers: CRET-ÚLCERAS-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No