Transcutaneous Application of Gaseous CO2

January 22, 2026 updated by: Helena Ban Frangez, University Medical Centre Ljubljana

The Effect of Transcutaneous Application of Gaseous CO2 on Diabetic Chronic Wound Healing

The research is designed to evaluate influence of transcutaneous application of CO2 (carbon dioxide) on chronic wound healing. Transcutaneous application of CO2 is known to have immediate effect on vasodilatation and elevates oxygen release from Hb via the Bohr effect. After repetition of the therapies neoangiogenesis is induced. Impairment of microcirculation is one of the causes of impared wound healing and improvement in circulation could have positive effect on wound healing, reduction of the wound area and granulation of the wound bed (Falanga score).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Transcutaneous application of gaseous CO2 showed to be a successful adjuvant therapy in treatment of chronic wounds in diabetic patients (PMID: 32633896). In this intervention technique, therapeutic concentrations of medical-grade CO2 are applied to the skin's surface in a safe, non-invasive manner. The main therapeutic mechanism is derived from the human body's natural response to locally increased CO2 concentration. Because vasodilatory capacity is impaired in diabetic foot, these mechanisms enhance local microvascular perfusion, thereby improving tissue oxygenation in patients with DFUs. Furthermore, although the researchers primarily focus on CO2 therapy as an intervention method, its efficacy is also suggested in preventing DFUs. We plan to enrole 120 patients, 80 into the study arm that will recieve CO2 therapy and 40 for a control group wothout CO2 therapy. All 120 patienrs will receive standard wound care. Aditionally, only study group will receive 20 treatments with CO2 (each workday for 4 weeks). Lower part of the body will be inserted into therapeutic wrap that is filled with 99.9% CO2 gas for 50 minutes. In both groups investigator will evaluate wound status (size, Falanga score of the wound bed) before first and after 4 weeks of treatment. Main outcome measure will be ratio of the completely heald wounds, reduction of the wound size in non healed wounds and status of the wound bed in non healed wounds after 4 weeks of treatment. Possible side effects of the CO2 therapy will be monitored.

Study Type

Interventional

Enrollment (Actual)

120

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Croatia
    • Croatia
      • Zagreb, Croatia, Croatia, 10000
        • Clinical Hospital Merkur, University Clinic for Diabetes, Endocrinology, and Metabolic Diseases Vuk Vrhovac, Dugi dol 4a, 10000 Zagreb
  • Slovenia
    • Ljubljana
      • Ljubljana, Ljubljana, Slovenia, 1000
        • UMCLjubljana
    • Slovenia
      • Novo Mesto, Slovenia, Slovenia, 8000
        • General hospital Novo mesto

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • confirmed diagnosis of DM Type 1 or Type 2,
  • confirmed diagnosis of a non-healing DFU without clinical signs of infection,
  • being able to provide informed consent for the participation, and

Exclusion Criteria:

  • patients with severe comorbidities: deep vein thrombosis, chronic kidney diseases grade III and IV, chronic heart diseases NYHA (New York Heart Association) III and IV, patients with known malignant diseases, patients with progressive infection, signs of systemic infection with elevated inflammatory markers or osteomyelitis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: CO2 treated
Patients receiving treatment with transcutaneous application of gaseous CO2 on lower limbs
Other: Transcutaneous CO2 application

Patients lie on examination tables. Lower extremities of the patients are isolated in a therapeutic wrap (single use, low-density, made from biocompatible polyethylene), sealed at the waist. After this, air is first pumped out of the therapeutic wrap, then the wrap was filled with 99.9% CO2 gas. The therapy lasts for 50 minutes.

Each patient from the study group will receive CO2 therapies - four weeks (meaning 20 CO2 therapies that were performed on workdays only).
No Intervention: control
Patients receiving standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ratio of completely healed wounds
Time Frame: after 4 weeks of therapy with CO2 or standard of care
The ratio of the completely healed wounds without exudate on 2 consecutive visits
after 4 weeks of therapy with CO2 or standard of care

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
reduction of the wound size of the unhealed wounds
Time Frame: after 4 weeks of therapy with CO2 or standard of care
the ratio of the reduction of the wound size in wound that are not completely helaed after 4 weeks of treatment
after 4 weeks of therapy with CO2 or standard of care

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Centre Ljubljana

Investigators

  • Principal Investigator: Igor Frangez, PhD, MD, DDS, UCMLjubljana

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2023

Primary Completion (Actual)

June 30, 2025

Study Completion (Actual)

September 22, 2025

Study Registration Dates

First Submitted

September 6, 2020

First Submitted That Met QC Criteria

September 17, 2020

First Posted (Actual)

September 23, 2020

Study Record Updates

Last Update Posted (Actual)

January 26, 2026

Last Update Submitted That Met QC Criteria

January 22, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UMCLjubljana CO2 application

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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