Burns, Wound Healing
Conditions
Keywords
Wound Healing, Burns, HIF-1, CAC
Brief summary
This research is being done to increase knowledge about wound healing and different factors that may affect healing in burn patients.
Detailed description
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.
Interventions
GENETICHealthy volunteers
Comparison of healthy volunteers to burn wounded volunteers
OTHERBurn volunteers
Comparison of burn wounded volunteers to healthy volunteers
Sponsors
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Johns Hopkins University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Eligibility
Sex/Gender
ALL
Age
14 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Recruitment of patients at the Johns Hopkins Regional Burn Center for study will be based upon the following clinical criteria: * Second degree scald burn of 10 cm2 * Age between 14 to 75 years * Burn area equal or less than 95% of Burn Surface Area (BSA) * Body temperature between 98.5 and 101 degree F * Informed consent for enrolment into study * Spanish speaking patients will be included when we have a Spanish consent form available.
Exclusion criteria
* First and third degree burn wounds * Hemodynamic instability (SBP below 100, Heart Rate (HR) over 100, urine output less than 30 ml/hour * Area of burn over 20% of BSA * Hypothermia T\<98.5 or Hyperthermia T\>101 degree F * Urine output less than 30 ml/hour * Serum albumin less than 3 mg/ml. * Subjects weighing less than 50 kg.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Volunteers Healthy volunteers with no burn wounds
Healthy volunteers: Comparison of healthy volunteers to burn wounded volunteers | 10 |
| Burn Volunteer Burn wounded volunteers
Burn volunteers: Comparison of burn wounded volunteers to healthy volunteers | 31 |
| Total | 41 |
Baseline characteristics
| Characteristic | Burn Volunteer | Total | Healthy Volunteers |
|---|---|---|---|
| Age, Customized >=14, <=75 | 31 Participants | 41 Participants | 10 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 31 participants | 41 participants | 10 participants |
| Sex: Female, Male Female | 7 Participants | 10 Participants | 3 Participants |
| Sex: Female, Male Male | 24 Participants | 31 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 31 |
| other Total, other adverse events | 0 / 10 | 0 / 31 |
| serious Total, serious adverse events | 0 / 10 | 0 / 31 |
Outcome results
Primary
Mean of Circulating Angiogenic Cells in the Blood of Individuals Who Have Sustained a Burn Injury
Tissue samples were harvested from healthy volunteers and participants who sustained burns. CACs were isolated and counted under fluorescence microscopy.
Time frame: 0 to 24 hours post-operative
Population: Data was only collected for the experimental arm for this outcome measure to assess the change in amount of CACs after burn injury as time progressed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Burn Volunteer | Mean of Circulating Angiogenic Cells in the Blood of Individuals Who Have Sustained a Burn Injury | 6500 cells per standard well |
Primary
Mean of Circulating Angiogenic Cells in the Blood of Individuals Who Have Sustained a Burn Injury
Tissue samples were harvested from healthy volunteers and participants who sustained burns. CACs were isolated and counted under fluorescence microscopy.
Time frame: 49 to 72 hours post-operative
Population: Data only collected for the experimental arm for this outcome measure to assess the change in amount of CACs after burn injury as time progressed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Burn Volunteer | Mean of Circulating Angiogenic Cells in the Blood of Individuals Who Have Sustained a Burn Injury | 5000 cells per standard well |
Primary
Mean of Circulating Angiogenic Cells in the Blood of Individuals Who Have Sustained a Burn Injury
Tissue samples were harvested from healthy volunteers and participants who sustained burns. CACs were isolated and counted under fluorescence microscopy.
Time frame: 73 hours to 6 weeks post-operative
Population: Data was only collected for the experimental arm for this outcome measure to assess the change in amount of CACs after burn injury as time progressed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Burn Volunteer | Mean of Circulating Angiogenic Cells in the Blood of Individuals Who Have Sustained a Burn Injury | 3500 cells per standard well |
Primary
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
Tissue samples were harvested from healthy volunteers and participants who sustained burns. CACs were isolated and counted under fluorescence microscopy.
Time frame: baseline
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Healthy Volunteers | 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 | 4,000 cells per standard well |
| Burn Volunteer | 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 | 6,500 cells per standard well |