Prospective Clinical Trials on Skin Wound Healing in Young and Aged Individuals

Diabetes Mellitus Clinical Trial

— RESOLVE  

Official title:

Pilot Study of Prospective Clinical Trials on Skin Wound Healing in Young and Aged Individuals

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01040104
• Other study ID #: FP7-202047.WP.2.1-2.2-2.4
• Secondary ID: MUW-EK-Nr_015/20
• Status: Completed
• Phase: N/A
• First received: December 28, 2009
• Last updated: November 10, 2013
• Start date: July 2009

Study information

• Verified date: November 2013
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Ethikkommission
• Study type: Observational

Clinical Trial Summary

Regular wound healing follows a well-ordered sequence of overlapping phases: inflammation, proliferation, maturation and remodelling.

In the young, damage to an organ mostly triggers fully regenerative mechanisms called "primary" wound healing. Repeated damage in young individuals may cause "secondary" wound healing eg. scar formation reflecting a rescue program, in which reorganisation has failed.

Organ failure in the ageing organism is characterized by a progressive loss of its capability to achieve an orderly reactivation of organ repair, and results in a combination of chronic inflammation and fibroproliferative, non-regenerative repair affecting several organs, including lung, liver and skin.

RESOLVE's objective is to identify, characterize, and validate molecular targets responsible for shifting primary organ repair towards fibroproliferative wound healing as a result of an age-dependent loss of regulatory control.

The structured approach is based on

• different forms of wound healing,

• different human diseases and

• different genetic backgrounds,

aiming to provide future diagnostic tools in various organs, to create transgenic animal test systems, and to identify molecular targets involved in fibroproliferative wound healing.

Description:

Cutaneous scars are frequently encountered conditions. The process of wound repair, however, is complicated, and various factors contribute to different types of scarring (eg. hypertrophic, atrophic).

WP 2.1: Regular skin repair

In elective plastic surgery most excised operative skin specimens are usually discarded, and represent an excellent opportunity of harvesting skin biopsies without additional invasive measures. This work package analyzes skin samples of individuals after elective plastic surgery with normal wound healing serving as control group.

WP 2.2: Skin repair with and without hypertrophic scar formation

A classic example of fibroproliferative repair in the skin is hypertrophic scarring classified as a dermal skin lesion, which is raised above skin level, stays within the confines of the initial wound and increases in size by pushing out the margins of the scar without invading the surrounding normal tissue.

Hypertrophic scarring is a condition commonly observed after burns and in regions of prolonged wound healing (>21 days). The underlying pathology of hypertrophic scarring, however, is poorly understood. Hypertrophic scars can be managed conservatively, and only require surgical intervention under special circumstances.

This work package analyzes the clinical and molecular response to a standard treatment regimen in skin regions with and without hypertrophic scars after skin injuries.

WP 2.4: Wound healing in normal and diabetic individuals

Diabetes mellitus is a known factor to cause impaired wound healing. Due to microangiopathic, macroangiopathic and other conditions resulting from atherosclerosis and peripheral neuropathy wound healing in diabetic individuals is usually delayed (hypotrophic, atrophic) and often complicated by immunosuppression and superinfections. The rising prevalence of diabetes mellitus in the elderly population makes it necessary to understand its related processes in relevant clinical wound models.

Split-thickness skin-grafting is a commonly applied technique in plastic surgery, and donor sites of previously uninjured skin regions spontaneously heal within two weeks, representing an ideal condition to monitor clinical and molecular changes in diseased vs. non-diseased states.

This work package analyzes skin repair in donor sites of split-thickness skin grafts in non-diabetic and diabetic individuals.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. primary completion date: July 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

WP2.1

Inclusion Criteria:

• age 18-45 and 55-85 years, respectively

Exclusion Criteria:

• past medical history of hypertrophic scarring or keloid disease

• cardiac disease adversely affecting peripheral blood flow

• active neoplastic disease

• immunosuppressive condition, congenital or acquired

• anemia

• autoimmune disorder

• acute or chronic renal failure

• liver cirrhosis or active hepatitis

• active substance-abuse disorder

• severe underweight (body mass index <16)

• endocrinological disorder

• pregnancy or lactation for women of child-bearing age

WP2.2

Inclusion Criteria:

• age 18-45 and 55-85 years, respectively

• normal and/or hypertrophic scars

• Baux score <100

Exclusion Criteria:

• sepsis

• electrical and/or chemical burn

• clinically significant wound infection in areas of planned biopsies

• cardiac disease adversely affecting peripheral blood flow

• active neoplastic disease

• immunosuppressive condition, congenital or acquired

• autoimmune disorder

• acute or chronic renal failure

• liver cirrhosis or active hepatitis

• active substance-abuse disorder

• severe underweight (body mass index <16)

• endocrinological disorder

• pregnancy or lactation for women of child-bearing age

WP 2.4

Inclusion Criteria:

• age 18-45 and 55-85 years, respectively

Exclusion Criteria:

• cardiac disease adversely affecting peripheral blood flow

• active neoplastic disease

• immunosuppressive condition, congenital or acquired

• anemia

• autoimmune disorder

• acute or chronic renal failure

• liver cirrhosis or active hepatitis

• substance-abuse disorder

• severe underweight (body mass index <16)

• thyroid function disorder

• pregnancy or lactation for women of child-bearing age

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Age
• Cicatrix, Hypertrophic
• Diabetes Mellitus
• Fibrosis
• Hypertrophy

Intervention

Other:
• Skin sample
Taken from regularly discarded tissue during routine operation
• Skin biopsy
Skin biopsy from regions exhibiting normal and/or hypertrophic scarring at day 0 and day 90
• Skin biopsy
Biopsy from skin graft harvest site during routine operation on day 0 and follow-up on day 90
• Blood taking
Blood taking on day 0
• Blood taking
Blood taking on day 90

Locations

Country	Name	City	State
Austria	Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna	Vienna

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of Vienna	European Union

Country where clinical trial is conducted

Austria, 

References & Publications (14)

Ashcroft GS, Mills SJ, Ashworth JJ. Ageing and wound healing. Biogerontology. 2002;3(6):337-45. Review. — View Citation

Blakytny R, Jude E. The molecular biology of chronic wounds and delayed healing in diabetes. Diabet Med. 2006 Jun;23(6):594-608. Review. — View Citation

Bombaro KM, Engrav LH, Carrougher GJ, Wiechman SA, Faucher L, Costa BA, Heimbach DM, Rivara FP, Honari S. What is the prevalence of hypertrophic scarring following burns? Burns. 2003 Jun;29(4):299-302. — View Citation

Crooks A. How does ageing affect the wound healing process? J Wound Care. 2005 May;14(5):222-3. Review. — View Citation

Deitch EA, Wheelahan TM, Rose MP, Clothier J, Cotter J. Hypertrophic burn scars: analysis of variables. J Trauma. 1983 Oct;23(10):895-8. — View Citation

Gangemi EN, Gregori D, Berchialla P, Zingarelli E, Cairo M, Bollero D, Ganem J, Capocelli R, Cuccuru F, Cassano P, Risso D, Stella M. Epidemiology and risk factors for pathologic scarring after burn wounds. Arch Facial Plast Surg. 2008 Mar-Apr;10(2):93-102. doi: 10.1001/archfaci.10.2.93. — View Citation

Gosain A, DiPietro LA. Aging and wound healing. World J Surg. 2004 Mar;28(3):321-6. Epub 2004 Feb 17. Review. — View Citation

Gottrup F, Agren MS, Karlsmark T. Models for use in wound healing research: a survey focusing on in vitro and in vivo adult soft tissue. Wound Repair Regen. 2000 Mar-Apr;8(2):83-96. Review. — View Citation

Izadi K, Ganchi P. Chronic wounds. Clin Plast Surg. 2005 Apr;32(2):209-22. Review. — View Citation

Komesu MC, Tanga MB, Buttros KR, Nakao C. Effects of acute diabetes on rat cutaneous wound healing. Pathophysiology. 2004 Oct;11(2):63-67. — View Citation

Mustoe TA, Cooter RD, Gold MH, Hobbs FD, Ramelet AA, Shakespeare PG, Stella M, Téot L, Wood FM, Ziegler UE; International Advisory Panel on Scar Management. International clinical recommendations on scar management. Plast Reconstr Surg. 2002 Aug;110(2):560-71. Review. — View Citation

Niessen FB, Spauwen PH, Schalkwijk J, Kon M. On the nature of hypertrophic scars and keloids: a review. Plast Reconstr Surg. 1999 Oct;104(5):1435-58. Review. — View Citation

Oliveira GV, Chinkes D, Mitchell C, Oliveras G, Hawkins HK, Herndon DN. Objective assessment of burn scar vascularity, erythema, pliability, thickness, and planimetry. Dermatol Surg. 2005 Jan;31(1):48-58. — View Citation

Rockwell WB, Cohen IK, Ehrlich HP. Keloids and hypertrophic scars: a comprehensive review. Plast Reconstr Surg. 1989 Nov;84(5):827-37. Review. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to wound healing / Scar maturation		day14, day90, day180	No

External Links

•   Ethics Committee of the Medical University of Vienna and the Vienna General Hospital
•   Working group link (RESOLVE, European Commission Project)