Adjunctive Hyperbaric Oxygen Therapy (HBOT) for Lower Extermity Diabetic Ulcer:
|ClinicalTrials.gov Identifier: NCT03675269|
Recruitment Status : Withdrawn (Study was moved to another location with involvement of different researchers)
First Posted : September 18, 2018
Last Update Posted : February 28, 2019
|First Submitted Date ICMJE||August 27, 2018|
|First Posted Date ICMJE||September 18, 2018|
|Last Update Posted Date||February 28, 2019|
|Actual Study Start Date ICMJE||September 5, 2018|
|Estimated Primary Completion Date||September 2019 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Change in wound size [ Time Frame: 4 years ]
The change of wound size at 4 weeks (granulation formation) as measured by the Silhouette three dimensional photography
|Original Primary Outcome Measures ICMJE||Same as current|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Adjunctive Hyperbaric Oxygen Therapy (HBOT) for Lower Extermity Diabetic Ulcer:|
|Official Title ICMJE||Adjunctive Hyperbaric Oxygen Therapy (HBOT) for Lower Extermity Diabetic Ulcer: A Prospective Double-Blind, Randomized Control Clinical Trail|
Diabetic foot ulcers are associated with high risk of amputation. About 50% of patients undergoing non-traumatic lower limb amputations are diabetics5. The 5-year amputation rate is estimated to be 19% with a mean time to amputation 58 months since the onset of an diabetic foot ulcer6.Because infection and tissue hypoxia are the major contributing factors for non-healing diabetic foot ulcers, hyperbaric oxygen therapy (HBO) carries a potential benefit for treating these problematic wounds that do not respond to standard therapy.
The role of oxygen in the wound healing cascade and subsequent combatting action against bacterial invasion, especially anaerobes, is well documented.14 Delayed or arrested healing and the development of infection is a direct result from decreased perfusion and poor oxygenation of tissue.15 The presence of wound hypoxia is an major etiological pathway in the development of chronic non-healing diabetic foot ulcers
1 KHUH Research Center
The Premise of the study:
Hyperbaric Oxygen as adjunctive therapy is effective towards the healing of diabetic lower extremity ulcers and has a role to play in major amputation prevention for persons with Diabetes Mellitus.
Title of the project:
Adjunctive Hyperbaric Oxygen Therapy (HBOT) for Lower Extremity Diabetic Ulcers: A Prospective, Double-Blind, Randomized, Controlled Clinical Trial Background Diabetes Mellitus is a major health problem with significant morbidity and mortality. The number of people with diabetes mellitus worldwide is estimated at 285 million in 2010; and expected to increase to 438 million by 20301. In western countries, like the United Kingdom, diabetic foot ulcers are the most commonly found chronic wound2. A diabetic foot ulcer is defined as a 'full thickness' lesion of the skin, that is, a wound penetrating through the dermis below the ankle joint3. The lifetime risk of developing foot ulcers in diabetics is estimated to be 15%4. These ulcers may heal with proper wound care, but some may become chronic and others may lead to amputation. These different outcomes are influenced by several risk factors including, among others, peripheral arterial disease (ischemia), peripheral neuropathy, mechanical foot deformity, poor foot care and inappropriate shoe wear.
Diabetic foot ulcers are associated with high risk of amputation. About 50% of patients undergoing non-traumatic lower limb amputations are diabetics5. The 5-year amputation rate is estimated to be 19% with a mean time to amputation 58 months since the onset of an diabetic foot ulcer6.Because infection and tissue hypoxia are the major contributing factors for non-healing diabetic foot ulcers, hyperbaric oxygen therapy (HBO) carries a potential benefit for treating these problematic wounds that do not respond to standard therapy7.
Vascular: Approximately 35% of diabetic foot ulcers result from peripheral vasculopathy with an additional 15-20% caused by mixed neuropathic-vasculopathic pathology8. There is an accelerated development of atherosclerosis in the distal arteries (tibial and peroneal arteries) of diabetic patients with the dorsalis pedis artery often spared. Abnormal smooth muscle tone and decreased perfusion exacerbate these changes. On a macrovascular level, thickening of the basement membrane and abnormal endothelial function is often found. Tissue ischemia may be worsened by capillary thrombosis and by impaired neurogenic control.9 The microcirculation of diabetic patients exhibits characteristic structural changes such as the reduction in the size of capillaries and thickening in basement membrane that impairs the normal hyperemic or vasodilatory response to injury10, 11 and interferes with transportation of nutrients and oxygen. Arterial thrombosis commonly develops in the presence of pre-existing atherosclerotic 2 changes in the vascular endothelium, as a result of low blood flow and increased blood viscosity or a pro-coagulative state. All of these changes are exacerbated by a smoking habit (cigarettes, cigars or water pipes) by inducing peripheral vasoconstriction that reduces available oxygen to tissue by 20-30% per cigarette for one hour.12 It induces alterations in lipid metabolism, increases platelet aggregation, and increase blood viscosity.12 Pressure: Peripheral neuropathy is the most common cause of foot ulcers and is present in 78% of the ulcer formation pathway.8 Foot deformity is the most common underlying cause and that is leading to unequal pressure redistribution and subsequent ulceration. Poor glycemic control and poor glycemic control increase the risk of neuropathy and is directly linked to the duration of living with diabetes (>15 years carrying a higher risk for developing neuropathy13), manifesting in all three components of the nervous system (autonomic, motor and sensory).
Autonomic neuropathy of the foot results in loss of sweat and oil gland function leading to dry cracked skin prone to bacterial infections; the loss of sympathetic vascular tone that leads to vasodilatation and the development of edema8.
Motor neuropathy causes loss of nerve supply to the intrinsic foot muscles with subsequent imbalance of the long flexor and extensor tendons. This produces an anatomic foot deformity with hyperextension of the toes, dropdown of the metatarsal heads and distal movement of the protective fat pad leading to pressure imbalance, callus formation and underlying skin breakdown.
In sensory neuropathy the loss of the protective components of the foot is rendering patients unaware of repeated traumas and small injury as a pain response is absent. A wound remain undetected, worsen, becomes secondarily infected with the patient usually late in presenting to formal health care, adding to the severity of the foot condition on assessment.
The role of oxygen in the wound healing cascade and subsequent combatting action against bacterial invasion, especially anaerobes, is well documented.14 Delayed or arrested healing and the development of infection is a direct result from decreased perfusion and poor oxygenation of tissue.15 The presence of wound hypoxia is an major etiological pathway in the development of chronic non-healing diabetic foot ulcers.16
Measurement of tissue oxygenation is done with transcutaneous oximetry (TcPO2) and provides a simple, noninvasive diagnostic technique for an objective assessment of local tissue perfusion and oxygenation.17 TcPO2 measurements are frequently used in the assessment of diabetic ulcers to:
Objectives of the study:
Study aim and objectives The aim of this study is to determine the effectiveness of 30 sessions of adjunctive hyperbaric oxygen therapy on the healing rate of diabetic lower extremity ulcers.
To compare between the treatment and control group:
The reduction of wound size at 4 weeks (granulation formation) as measured by the Silhouette three dimensional photography Time to achieve 80% wound surface reduction as measured by the Silhouette trajectory Time to achieve bipedal ambulation on an offloading device crossing the ankle joint The level of neovascularization achieved as measured by transcutaneous oximetry The proportion of patients ending up with a below knee amputation.
Determine the TCpO2 criteria by which treatment response could be measured.Determine the TCpO2 criteria by which optimal treatment is assessed (to indicate completion of therapy).
Evaluate the role of minor amputations (one or more toes up to the mid foot) in saving the major limb (integrity of the knee and ankle joint) Evaluate the role of HBO in resolution of infection/osteomyelitis in conjunction with appropriate systemic antibiotics.
To determine and describe the side-effects of HBO therapy. 4 Improvement of quality of life with particular attention to pain. Setting: The hyperbaric and wound care unit of King Hamad University hospital, Kingdom of Bahrain
Design: A parallel prospective double-blind randomized placebo-controlled trial.
Sample size: 100-120 patients equally divided between the two treatment arms Sampling technique: Randomization by sealed envelope method to either Arm A or Arm B, both blinded to all apart from the primary researcher.
Timeframe of the study: 12-24 months in order to fill the appropriate sample size on an 80% confidence interval
Data Collection methods, instruments used and measurements:
Data management and analysis plan:
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Not Applicable|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
|Study Arms ICMJE||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Withdrawn|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Estimated Study Completion Date ICMJE||September 2019|
|Estimated Primary Completion Date||September 2019 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages ICMJE||18 Years and older (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Not Provided|
|Removed Location Countries|
|NCT Number ICMJE||NCT03675269|
|Other Study ID Numbers ICMJE||KingHamadUHBahrain|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||King Hamad University Hospital, Bahrain|
|Study Sponsor ICMJE||King Hamad University Hospital, Bahrain|
|Collaborators ICMJE||University of Stellenbosch|
|Investigators ICMJE||Not Provided|
|PRS Account||King Hamad University Hospital, Bahrain|
|Verification Date||February 2019|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP