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

NCT ID: NCT01040104

Last Updated: 2013-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

51 participants

Study Classification

OBSERVATIONAL

Study Start Date

2009-07-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Age Cicatrix, Hypertrophic Fibrosis Diabetes Mellitus

Keywords

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wound healing hypertrophic scar skin transplantation diabetes mellitus

Study Design

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Study Time Perspective

PROSPECTIVE

Study Groups

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Regular wound healing, young

Regular skin repair, controlled wound healing conditions in young individuals

Skin sample

Intervention Type OTHER

Taken from regularly discarded tissue during routine operation

Blood taking

Intervention Type OTHER

Blood taking on day 0

Regular wound healing, aged

Regular skin repair, controlled wound healing conditions in aged individuals

Skin sample

Intervention Type OTHER

Taken from regularly discarded tissue during routine operation

Blood taking

Intervention Type OTHER

Blood taking on day 0

Hypertrophic scarring, young

Skin repair with and without hypertrophic scarring in young individuals

Skin biopsy

Intervention Type OTHER

Skin biopsy from regions exhibiting normal and/or hypertrophic scarring at day 0 and day 90

Blood taking

Intervention Type OTHER

Blood taking on day 0

Blood taking

Intervention Type OTHER

Blood taking on day 90

Hypertrophic scarring, aged

Skin repair with and without hypertrophic scarring in aged individuals

Skin biopsy

Intervention Type OTHER

Skin biopsy from regions exhibiting normal and/or hypertrophic scarring at day 0 and day 90

Blood taking

Intervention Type OTHER

Blood taking on day 0

Blood taking

Intervention Type OTHER

Blood taking on day 90

Non-diabetic, young

Skin repair in non-diabetic young individuals

Skin biopsy

Intervention Type OTHER

Biopsy from skin graft harvest site during routine operation on day 0 and follow-up on day 90

Blood taking

Intervention Type OTHER

Blood taking on day 0

Blood taking

Intervention Type OTHER

Blood taking on day 90

Non-diabetic, aged

Skin repair in non-diabetic aged individuals

Skin biopsy

Intervention Type OTHER

Biopsy from skin graft harvest site during routine operation on day 0 and follow-up on day 90

Blood taking

Intervention Type OTHER

Blood taking on day 0

Blood taking

Intervention Type OTHER

Blood taking on day 90

Diabetic, young

Skin repair in young diabetic individuals

Skin biopsy

Intervention Type OTHER

Biopsy from skin graft harvest site during routine operation on day 0 and follow-up on day 90

Blood taking

Intervention Type OTHER

Blood taking on day 0

Blood taking

Intervention Type OTHER

Blood taking on day 90

Diabetic, aged

Skin repair in aged diabetic individuals

Skin biopsy

Intervention Type OTHER

Biopsy from skin graft harvest site during routine operation on day 0 and follow-up on day 90

Blood taking

Intervention Type OTHER

Blood taking on day 0

Blood taking

Intervention Type OTHER

Blood taking on day 90

Interventions

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Skin sample

Taken from regularly discarded tissue during routine operation

Intervention Type OTHER

Skin biopsy

Skin biopsy from regions exhibiting normal and/or hypertrophic scarring at day 0 and day 90

Intervention Type OTHER

Skin biopsy

Biopsy from skin graft harvest site during routine operation on day 0 and follow-up on day 90

Intervention Type OTHER

Blood taking

Blood taking on day 0

Intervention Type OTHER

Blood taking

Blood taking on day 90

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

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


* age 18-45 and 55-85 years, respectively
* normal and/or hypertrophic scars
* Baux score \<100


* 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


* 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


* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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European Union

OTHER

Sponsor Role collaborator

Medical University of Vienna

OTHER

Sponsor Role lead

Responsible Party

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David Lumenta, MD

Dr

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lars P Kamolz, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

MUW

Locations

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Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna

Vienna, Vienna, Austria

Site Status

Countries

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Austria

References

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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.

Reference Type BACKGROUND
PMID: 18347236 (View on PubMed)

Izadi K, Ganchi P. Chronic wounds. Clin Plast Surg. 2005 Apr;32(2):209-22. doi: 10.1016/j.cps.2004.11.011.

Reference Type BACKGROUND
PMID: 15814118 (View on PubMed)

Blakytny R, Jude E. The molecular biology of chronic wounds and delayed healing in diabetes. Diabet Med. 2006 Jun;23(6):594-608. doi: 10.1111/j.1464-5491.2006.01773.x.

Reference Type BACKGROUND
PMID: 16759300 (View on PubMed)

Komesu MC, Tanga MB, Buttros KR, Nakao C. Effects of acute diabetes on rat cutaneous wound healing. Pathophysiology. 2004 Oct;11(2):63-67. doi: 10.1016/j.pathophys.2004.02.002.

Reference Type BACKGROUND
PMID: 15364115 (View on PubMed)

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. doi: 10.1097/00006534-199910000-00031. No abstract available.

Reference Type BACKGROUND
PMID: 10513931 (View on PubMed)

Rockwell WB, Cohen IK, Ehrlich HP. Keloids and hypertrophic scars: a comprehensive review. Plast Reconstr Surg. 1989 Nov;84(5):827-37. doi: 10.1097/00006534-198911000-00021. No abstract available.

Reference Type BACKGROUND
PMID: 2682703 (View on PubMed)

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. doi: 10.1046/j.1524-475x.2000.00083.x.

Reference Type BACKGROUND
PMID: 10810034 (View on PubMed)

Ashcroft GS, Mills SJ, Ashworth JJ. Ageing and wound healing. Biogerontology. 2002;3(6):337-45. doi: 10.1023/a:1021399228395.

Reference Type BACKGROUND
PMID: 12510172 (View on PubMed)

Gosain A, DiPietro LA. Aging and wound healing. World J Surg. 2004 Mar;28(3):321-6. doi: 10.1007/s00268-003-7397-6. Epub 2004 Feb 17.

Reference Type BACKGROUND
PMID: 14961191 (View on PubMed)

Crooks A. How does ageing affect the wound healing process? J Wound Care. 2005 May;14(5):222-3. doi: 10.12968/jowc.2005.14.5.26777.

Reference Type BACKGROUND
PMID: 15909438 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 6632013 (View on PubMed)

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. doi: 10.1016/s0305-4179(03)00067-6.

Reference Type BACKGROUND
PMID: 12781605 (View on PubMed)

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. doi: 10.1111/j.1524-4725.2005.31004.

Reference Type BACKGROUND
PMID: 15720096 (View on PubMed)

Mustoe TA, Cooter RD, Gold MH, Hobbs FD, Ramelet AA, Shakespeare PG, Stella M, Teot 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. doi: 10.1097/00006534-200208000-00031.

Reference Type BACKGROUND
PMID: 12142678 (View on PubMed)

Related Links

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http://www.meduniwien.ac.at/ethik/index.htm

Ethics Committee of the Medical University of Vienna and the Vienna General Hospital

Other Identifiers

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MUW-EK-Nr_015/2009

Identifier Type: OTHER

Identifier Source: secondary_id

FP7-202047.WP.2.1-2.2-2.4

Identifier Type: -

Identifier Source: org_study_id