Hyperbaric Oxygenation in Diabetic Ulcer

Study Overview
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Brief Summary
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Hyperbaric oxygenation (HBO) involves breathing of 100% oxygen under elevated ambient pressure. In correlation to the pressure level oxygen dissolves in the plasma resulting in an increase of total oxygen in the body. The elevated tissue levels of oxygen may persist for hours, instigating healing processes in wounds caused by disturbances in of perfusion in small vessels, a condition often found in patient with diabetes. We plan a prospective, double-blind randomized clinical study in 80 patients with chronic diabetic ulcer. All will have optimum treatment of diabetes. The HBO group will be given HBO at 2.4 bar, 90 min., 30 sessions, controls will have sham HBO. Routine wound care will be identical in both groups. Before, during and after treatment (3, 6 and 12 months), a number of monitoring and imaging procedures will be done, cells in the bloodstream indicating improved healing will be determined. Hypothesis: HBO will instigate the healing process in the majority of patients with chronic diabetic leg ulcer, provided the patency of the large vessels is given.

Detailed Description
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We plan a prospective, double-blind randomized clinical study (phase III) in 80 patients with diabetes mellitus. All of them will receive the optimum metabolic treatment for their underlying disease. The treatment group will be administered HBO according to the problem wound schedule, the controls will have sham treatment in the hyperbaric chamber. Routine wound care (dressings, physiotherapy, antibiotics if necessary) will be identical in both groups and according to its clinical needs. Before treatment, indocyanine green videoangiography (ICG), transcutaneous (partial) oxygen pressure (TcPO2) and LifeViz 3D (three-dimensional medical imaging and reconstruction) documentation will be done and endothelial progenitor cells (EPC) as well as markers of bone metabolism will be determined in all patients. The measurements will be repeated according to the schedule during the treatment period and at controls after 3, 6 and 12 months.

Official Title
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Hyperbaric Oxygenation (HBO) in Chronic Diabetic Leg Ulcer.

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: Hyperbaric oxygen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diabetes mellitus Age between 18 and 80 years Chronic foot ulcer (up to Wagner scale III) Patency of large vessels tributary to region of wound Good outpatient diabetes management as verified by a specialized centre (HbA1c<8.5%; IFCC: 69mmol/mol). Exclusion Criteria: Clinically relevant obstruction of large vessels tributary to region of wound Non-adherence to diabetes therapy Pregnancy Reactive airway disease Radiographic evidence of pulmonary blebs or bullae Untreated pneumothorax History of seizures except childhood febrile seizures Cardiovascular instability Mechanical ventilator support Treatment with Bleomycin or Anthracyclin in history Unable to perform the Valsalva-procedure Participation as a subject in any other medical or biomedical research project; if previously involved as a subject, sufficient time must have elapsed to permit wash out of any investigational agent.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyperbaric oxygen<br>Problem-wound schedule: 2.4 atmospheres, 100% oxygen for 90 minutes, two 10 - minute breaks (patients breathing pressurized air from the chamber atmosphere) | Drug: Hyperbaric oxygen<br>* The treatment will be applied in a large walk-in drive-in hyperbaric chamber. Depending on their general condition, the patients will sit in comfortable chairs or remain in their own wheelchair or bed in relaxed position. They will be accompanied by a medical attendant or by a hyperbaric physician if necessary due to their general condition. Oxygen 100% will be distributed over a tight fitting oxygen-mask connected to the overboard-dumping system. The treatment will be administered according to the so-called problem-wound schedule once a day for six consecutive weeks. On weekends and on public holidays the patients will be off therapy.<br>* Other names: Hyperbaric oxygenation;|
| Placebo Comparator: Sham Hyperbaric oxygen<br>The patients will be transferred into the chamber like the treatment group. Instead of 100% oxygen they will breathe normal air through the tight fitting masks, at an ambient pressure of 1.1 bar. During the two 10 - minute breaks patients will breathe pressurized air from the chamber atmosphere. | Drug: Hyperbaric oxygen<br>* The treatment will be applied in a large walk-in drive-in hyperbaric chamber. Depending on their general condition, the patients will sit in comfortable chairs or remain in their own wheelchair or bed in relaxed position. They will be accompanied by a medical attendant or by a hyperbaric physician if necessary due to their general condition. Oxygen 100% will be distributed over a tight fitting oxygen-mask connected to the overboard-dumping system. The treatment will be administered according to the so-called problem-wound schedule once a day for six consecutive weeks. On weekends and on public holidays the patients will be off therapy.<br>* Other names: Hyperbaric oxygenation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICG (indocyanine green) video angiography | Change in ICG-adsorption measured by ICG video angiography from baseline to week/month xxx | Weeks 1-3, 6; Months 3, 6, 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High performance 3D LifeViz™ system | Change of size/configuration of wound from baseline to week/month xxx | Week 1-6; Months 3, 6, 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperbaric Oxygen, Diabetic ulcer, Wound healing, 3-D life-viz- system, Indocyanine green video angiography, Transcutaneous oxygen pressure, Endothelial progenitor cells