Testing an Innovative Biomarker: Expression of HIF-1α and Its Isoforms in the Blood and Skin Tissue of Major Burns

Burn Injuries Clinical Trial

— HIF  

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02870439
• Other study ID #: 2012-23
• Secondary ID: 2012-A00786-37
• Status: Recruiting
• Phase: N/A
• First received: August 12, 2016
• Last updated: August 16, 2016
• Start date: October 2012
• Est. completion date: October 2017

Study information

• Verified date: August 2016
• Source: Assistance Publique Hopitaux De Marseille
• Contact: Aurélie HAUTIER, MD
• Email: aurelie.hautier[@]ap-hm.fr
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

Burn injury with full-thickness skin damage that encompass large body surface areas can induce local and systemic perturbations that are costly in terms of human suffering as well as in strains on the health care system. Characterization of new major molecular biomarkers involved in this process creates significant diagnostic and therapeutic challenges.

Hypoxia-inducible factor-1 α (HIF-1 α) is a ubiquitously expressed heterodimeric transcription factor comprising an α and a β subunit. It was shown that under normoxic conditions, the HIF-1α subunit is ubiquitinated and degraded, whereas under hypoxic conditions, HIF-1α accumulates, dimerizes with HIF-1β, and activates the transcription of a spectrum of target genes encoding multiple angiogenic growth factors and cytokines of potential importance in wound healing. Seven isoforms of HIF-1α issued from alternative splicing have been identified.

The importance of HIF-1α in wound healing in animal models has been suggested by several studies. Indeed, diminished HIF-1 levels and activity have been documented in conditions of impaired wound healing. The literature review shows a marked reduction of HIF-1α levels in mice in case of burn wound skin that in the case of excisional cutaneous wound. Other studies have shown that the expression of HIF-1α was correlated with the extent and depth of the burns.

This study aims to improve the knowledge on the pathophysiological factors involved in the field of wound healing. The assumptions are based on results of studies done on mice, and this work aims to document these findings in humans.

Objective

The main objective of the study is to compare the variations of expression of HIF-1α measured in blood and skin tissue samples in three groups:

• Subjects with major burn wounds involving more than 20% of the total body surface area;

• Subjects with burn wounds smaller than 5% of total body surface area;

• Subjects with a skin wound after a surgical procedure requiring a skin resection.

Secondary objectives are to compare the expression levels of HIF-1α locally at the burn site to those observed in blood, to evaluate the expression of growth factors produced by HIF-1α target genes (VEGF and EPO) or playing a central role in the healing process (TGF-β1), and to assess the correlation between the expression of HIF-1α and the kinetics of wound healing of the subject rated by evaluation of time of donor sites complete epithelialization.

Material and Methods

We propose to create three groups:

• 15 patients with extensive third degree burns involving more than 20% of the total body surface area;

• 15 patients with less extensive third degree burns, involving less than 5% of body surface area;

• 15 patients with post-surgical wounds with skin resection. Skin and tissue specimens will be collected three times: day 0, 7 and 14 from burned patients (with more than 20% of the total body surface area and less than 5% of body surface area). Samples of skin tissue will be collected within the skin resection from patients with post-surgical wounds at day 0, blood samples will be collected at day 0 and 14.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: October 2017
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient with burn wounds

Exclusion Criteria:

• Patient with wounds coming from electrical or chemical burns

• Patient undergoing long term corticotherapy

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Burn Injuries
• Burns

Intervention

Other:
• Blood drawn

Locations

Country	Name	City	State
France	Assistance Publique Hôpitaux de Marseille	Marseille

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique Hopitaux De Marseille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	percentage of the variations of expression of HIF-1a		14 days	No