Transcutaneous CO₂ Therapy in Recurrent Hard-to-Heal Diabetic Foot Ulcers

NCT07418073 | Completed

• 1 other identifier: NM-DVS-CO2
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Recurrent and hard-to-heal diabetic foot ulcers (DFUs) represent a clinically challenging subgroup with delayed closure and frequent non-response to standard of care (SOC). Impaired local perfusion and superficial tissue hypoxia, commonly attributed to microcirculatory dysfunction, are proposed contributors to impaired wound-bed progression and prolonged healing trajectories in diabetes. Transcutaneous gaseous carbon dioxide (CO₂) therapy is a non-invasive adjunct intervention with a mechanistic rationale to modulate local microcirculation and tissue oxygenation; however, controlled clinical evidence in recurrent, hard-to-heal DFUs remains limited. This prospective, randomized, controlled, open-label, parallel-group clinical investigation compares transcutaneous CO₂ therapy plus SOC versus SOC alone over 4 weeks. The primary objective is to determine whether the proportion of completely healed DFUs at Week 4 differs between groups under a predefined healing confirmation procedure. Key secondary objectives include quantifying changes in superficial tissue oxygenation (StO₂) using hyperspectral imaging and assessing pain intensity (NPRS). Supportive outcomes include ulcer area reduction metrics and wound-bed appearance in unhealed.

Conditions

Ulcer Foot

Keywords

Diabetic foot ulcer; CO2 therapy; microcirculation

Outcome Measures

Primary Outcomes (1)

• complete ulcer healing

  full epitelization without exudate confirmed at 2 consecutive exams

  4 weeks

Secondary Outcomes (2)

• change in StO2

  4 weeks

• change in pain intensity (NPRS)

  4 weeks

Study Arms (2)

Standard of care + CO2 therapy

EXPERIMENTAL

Standard of care (3 times weekly) + transcutaneous gaseous CO2 therapy 20 times (every weekday for 50 minutes)

Other: transcutaneous application of gaseous CO2 on lower part of the body

Standard of care

NO INTERVENTION

Standard of care (3 times weekly)

Interventions

transcutaneous application of gaseous CO2 on lower part of the body OTHER

Participants in the intervention group received SOC alongside 20 sessions of CO₂ therapy. These 50-minute sessions were administered once daily on weekdays (Monday-Friday) over a 4-week period. CO₂ therapies were performed using the medical device. The participant's lower body was sealed in a single-use, biocompatible, medical-grade wrap. The wrap was filled with medical-grade CO₂ to a 99.9% concentration for a 50-minute session. After 50 minutes, CO₂ was pumped out and the wrap removed.

Standard of care + CO2 therapy

Eligibility Criteria

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

You may qualify if:

• diabetes mellitus type 1 or 2
• recurrent hard to heal DFU

You may not qualify if:

• KOPD stage IV
• CKD stage IV
• malignant diseases
• pregnancy
• infected ulcer at baseline
• inability to comply with visits

Sponsors & Collaborators

• University Medical Centre Ljubljana: lead

Study Sites (1)

UMC Ljubljana

Ljubljana, Slovenia, 1000, Slovenia

Location

Related Publications (2)

• Finzgar, M., Melik, Z., in Cankar, K. (2015). Effect of transcutaneous application of gaseous carbon dioxide on cutaneous microcirculation. Clinical Hemorheology and Microcirculation, 60(4), 423-435. https://doi.org/10.3233/CH-141898

  BACKGROUND

• Macura, M., Ban Frangež, H., Cankar, K., Finžgar, M., in Frangež, I. (2020). The effect of transcutaneous application of gaseous CO2 on diabetic chronic wound healing-A double-blind randomized clinical trial. International Wound Journal, 17(5), 1182-1190. https://doi.org/10.1111/iwj.13436

  BACKGROUND

MeSH Terms

Conditions

Foot Ulcer; Diabetic Foot

Condition Hierarchy (Ancestors)

Foot Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Leg Ulcer; Skin Ulcer; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases; Diabetic Neuropathies

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: Assoc. prof. Igor Frangež, MD, DDS, PhD, EAFWH

Study Record Dates

• First Submitted: February 10, 2026
• First Posted: February 18, 2026
• Study Start: September 1, 2024
• Primary Completion: March 20, 2025
• Study Completion: August 30, 2025
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1)