Clinical trial NCT00796627: Hypoxia-inducible Factor-1 (HIF-1) Regulated Circulating Angiogenic Cells (CACs) Recruitment in Burn Wound Healing
Official title: HIF-1 Regulated Circulating Angiogenic Cell Recruitment in Burn Wound Healing
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Wound Healing
Burns
Keywords: Wound Healing
Burns
HIF-1
CAC
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2008-11-24
Enrollment: 41
Sex: ALL
Minimum age (years): 14
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: baseline
measure: Mean of Circulating Angiogenic Cells in the Blood of Individuals Who Have Sustained a Burn Injury
timeFrame: 0 to 24 hours post-operative
measure: Mean of Circulating Angiogenic Cells in the Blood of Individuals Who Have Sustained a Burn Injury
timeFrame: 49 to 72 hours post-operative
measure: Mean of Circulating Angiogenic Cells in the Blood of Individuals Who Have Sustained a Burn Injury
timeFrame: 73 hours to 6 weeks post-operative
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: John Harmon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhang X, Wei X, Liu L, Marti GP, Ghanamah MS, Arshad MJ, Strom L, Spence R, Jeng J, Milner S, Harmon JW, Semenza GL. Association of increasing burn severity in mice with delayed mobilization of circulating angiogenic cells. Arch Surg. 2010 Mar;145(3):259-66. doi: 10.1001/archsurg.2009.285.