Hypoxia-inducible Factor-1 (HIF-1) Regulated Circulating Angiogenic Cells (CACs) Recruitment in Burn Wound Healing
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|ClinicalTrials.gov Identifier: NCT00796627|
Recruitment Status : Terminated (unable to recruit enough patients)
First Posted : November 24, 2008
Results First Posted : September 29, 2017
Last Update Posted : September 29, 2017
|Condition or disease||Intervention/treatment||Phase|
|Wound Healing Burns||Genetic: Healthy volunteers Other: Burn volunteers||Not Applicable|
Burn injuries represent a major public health problem, requiring medical attention for more than one million Americans annually. Despite therapeutic advances, non-healing burn wounds and excessive scarring still result in significant long term physical and psychosocial morbidity. In this study we propose to perform clinical and research to study the role of circulating angiogenic cells (CAC) in promoting burn wound healing.
CAC's have been shown to contribute to vascularization and tissue repair in a number of animal models of tissue injury ischemia and mobilization of CACs into the peripheral blood has been demonstrated in burn wound patients.
We hypothesize that primary healing of burn wounds is dependent on repair of damaged vasculature, and that bone marrow derived stem cells, circulating angiogenic cells (CAC), play a critical role in the healing process. Furthermore we propose that the transcription factor Hypoxia Inducible Factor 1 alpha (HIF 1 alpha) through production of peptide products of its downstream target genes directs the "homing" of CAC's to the wound where they participate in healing events. The first aim of this study is to correlate mobilization of CAC's into the blood stream with the success of burn wound healing.
CAC's have been shown to contribute to vascularization and tissue repair in a number of studies. The relationship between mobilization of CAC's and burn wound healing has not been examined. In addition to surveying CAC numbers in the peripheral blood, we will assay levels of the putative mediators of CAC mobilization: Vascular Endothelial Growth Factor (VEGF), Placenta Growth Factor (PLGF), and Stromal Cell-Derived Factor (SDF-1). We hypothesize that individuals who are able to mount a large and sustained mobilization of CAC's into the peripheral blood from the bone marrow, will be more likely to heal the injured vasculature and go on to primary healing. Individuals with an inadequate mobilization of CAC's will fail to repair the damaged vasculature in the wound and proceed to necrosis and "conversion" to third degree, necrotic burn wounds.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||41 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Masking Description:||Open Label|
|Official Title:||HIF-1 Regulated Circulating Angiogenic Cell Recruitment in Burn Wound Healing|
|Study Start Date :||December 2006|
|Actual Primary Completion Date :||April 2014|
|Actual Study Completion Date :||April 2014|
Sham Comparator: Healthy volunteers
Healthy volunteers with no burn wounds Volunteers donate blood that will be studied in comparison to patients who have sustained burns. The circulating "bone marrow stem cells" will be counted and compared to the levels in burn patients. Six 12 ml tubes will be taken for the study. You will not be compensated. But you will be helping to advance science if you join the study.
Genetic: Healthy volunteers
Comparison of healthy volunteers to burn wounded volunteers
Active Comparator: Burn volunteer
To recruit burn wound patients with defined clinical criteria for study. A second-degree burn of at least 10 cm2 to up to 95% BSA; age = 14-75 years; BP > 100 mm Hg systolic; heart rate < 100 beats/minute; urine output > 30 ml/hour; area of burn < 20% of BSA; body temperature = 98.5-101 degrees Fahrenheit; serum albumin > 3 mg/ml; and informed consent. We will also obtain a history regarding the presence or absence of risk factors that may affect CAC numbers: hypertension > 1 year; smoking > 2 pack-years or within the last year; diabetes mellitus; and family history of premature coronary artery disease (men < 55 and women < 65 years of age).Six 12 ml tubes will be taken at 5 time points
Other: Burn volunteers
Comparison of burn wounded volunteers to healthy volunteers
Other Name: Burn wounds
- The Quantification of Circulating Angiogenic Cells in the Blood of Individuals Who Are Healthy Volunteers Compared to Those in Individuals Who Have Sustained a Burn Injury [ Time Frame: baseline ]Tissue samples were harvested from healthy volunteers and participants who sustained burns. CACs were isolated and counted under fluorescence microscopy.
- Mean of Circulating Angiogenic Cells in the Blood of Individuals Who Have Sustained a Burn Injury [ Time Frame: 0 to 24 hours post-operative ]Tissue samples were harvested from healthy volunteers and participants who sustained burns. CACs were isolated and counted under fluorescence microscopy.
- Mean of Circulating Angiogenic Cells in the Blood of Individuals Who Have Sustained a Burn Injury [ Time Frame: 49 to 72 hours post-operative ]Tissue samples were harvested from healthy volunteers and participants who sustained burns. CACs were isolated and counted under fluorescence microscopy.
- Mean of Circulating Angiogenic Cells in the Blood of Individuals Who Have Sustained a Burn Injury [ Time Frame: 73 hours to 6 weeks post-operative ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00796627
|United States, Maryland|
|Johns Hopkins Bayview Medical Center|
|Baltimore, Maryland, United States, 21224|
|Principal Investigator:||John Harmon, MD||Johns Hopkins University|