Transcutaneous Application of Gaseous CO2

NCT04561609 | Completed

• 1 other identifier: UMCLjubljana CO2 application
• Study Type: interventional
• Target: 120
• Locations: 2 countries
• Sites: 3

Brief Summary

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).

Conditions

Chronic Wound of the Lower Limb (Leg Ulcer or Foot Ulcer)

Keywords

transcutaneous CO2 application

Outcome Measures

Primary Outcomes (1)

• Ratio of completely healed wounds

  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 Outcomes (1)

• reduction of the wound size of the unhealed wounds

  after 4 weeks of therapy with CO2 or standard of care

Study Arms (2)

CO2 treated

ACTIVE COMPARATOR

Patients receiving treatment with transcutaneous application of gaseous CO2 on lower limbs

Other: Transcutaneous CO2 application

control

NO INTERVENTION

Patients receiving standard of care

Interventions

Transcutaneous CO2 application OTHER

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).

CO2 treated

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead

Study Sites (3)

Clinical Hospital Merkur, University Clinic for Diabetes, Endocrinology, and Metabolic Diseases Vuk Vrhovac, Dugi dol 4a, 10000 Zagreb

Zagreb, Croatia, 10000, Croatia

Location

UMCLjubljana

Ljubljana, Ljubljana, 1000, Slovenia

Location

General hospital Novo mesto

Novo Mesto, Slovenia, 8000, Slovenia

Location

Related Publications (4)

• Smith AG, Ramachandran P, Tripp S, Singleton JR. Epidermal nerve innervation in impaired glucose tolerance and diabetes-associated neuropathy. Neurology. 2001 Nov 13;57(9):1701-4. doi: 10.1212/wnl.57.9.1701.

  PMID: 11706115 BACKGROUND

• Sakai Y, Miwa M, Oe K, Ueha T, Koh A, Niikura T, Iwakura T, Lee SY, Tanaka M, Kurosaka M. A novel system for transcutaneous application of carbon dioxide causing an "artificial Bohr effect" in the human body. PLoS One. 2011;6(9):e24137. doi: 10.1371/journal.pone.0024137. Epub 2011 Sep 8.

  PMID: 21931656 BACKGROUND

• Macura M, Ban Frangez H, Cankar K, Finzgar M, Frangez I. The effect of transcutaneous application of gaseous CO2 on diabetic chronic wound healing-A double-blind randomized clinical trial. Int Wound J. 2020 Dec;17(6):1607-1614. doi: 10.1111/iwj.13436. Epub 2020 Jul 7.

  PMID: 32633896 BACKGROUND

• Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G, Malik RA, Spallone V, Vinik A, Bernardi L, Valensi P; Toronto Diabetic Neuropathy Expert Group. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010 Oct;33(10):2285-93. doi: 10.2337/dc10-1303.

  PMID: 20876709 BACKGROUND

MeSH Terms

Conditions

Leg Ulcer; Foot Ulcer

Condition Hierarchy (Ancestors)

Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases; Foot Diseases

Study Officials

• Igor Frangez, PhD, MD, DDS

  UCMLjubljana

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: assistant professor MD, PhD

Model Details: The use of transcutaneous application of gaseous CO2 for treatment of diabetic chronic wound. A Control group receives standard of care.

Study Record Dates

• First Submitted: September 6, 2020
• First Posted: September 23, 2020
• Study Start: May 15, 2023
• Primary Completion: June 30, 2025
• Study Completion: September 22, 2025
• Last Updated: January 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CR (1); SL (2)