Hyperbaric Oxygenation in Diabetic Ulcer

Hyperbaric Oxygenation (HBO) in Chronic Diabetic Leg Ulcer.

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.

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: Hyperbaric oxygen

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Styria
    • Graz, Styria, Austria, A-8036
      • Division of Thoracic and Hyperbaric Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hyperbaric oxygen; 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; 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.; Other Names: HBO; Hyperbaric oxygenation
Placebo Comparator: Sham Hyperbaric oxygen; 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; 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.; Other Names: HBO; Hyperbaric oxygenation

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endothelial progenitor cells	Modulation of number	Weeks 1-6, Months 3,6,12

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Investigators: Principal Investigator: Freyja M Smolle-Juettner, M.D., Medical University of Graz

Publications and helpful links

General Publications

• O'Reilly D, Pasricha A, Campbell K, Burke N, Assasi N, Bowen JM, Tarride JE, Goeree R. Hyperbaric oxygen therapy for diabetic ulcers: systematic review and meta-analysis. Int J Technol Assess Health Care. 2013 Jul;29(3):269-81. doi: 10.1017/S0266462313000263.
• Londahl M. Hyperbaric oxygen therapy as adjunctive treatment of diabetic foot ulcers. Med Clin North Am. 2013 Sep;97(5):957-80. doi: 10.1016/j.mcna.2013.04.004. Epub 2013 Jul 6.
• Kranke P, Bennett MH, Martyn-St James M, Schnabel A, Debus SE. Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst Rev. 2012 Apr 18;(4):CD004123. doi: 10.1002/14651858.CD004123.pub3.

Helpful Links

• The Division of Thoracic and Hyperbaric Surgery is part of the Medical University Graz

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2019
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: January 20, 2014
• First Submitted That Met QC Criteria: January 20, 2014
• First Posted (Estimate): January 22, 2014

Study Record Updates

• Last Update Posted (Actual): May 20, 2019
• Last Update Submitted That Met QC Criteria: May 17, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Wound healing; Hyperbaric Oxygen; Diabetic ulcer; 3-D life-viz- system; Indocyanine green video angiography; Transcutaneous oxygen pressure; Endothelial progenitor cells
• Additional Relevant MeSH Terms: Pathologic Processes; Ulcer
• Other Study ID Numbers: 24-265ex11/12; 2012-001436-57 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No