Genetic and Epigenetic Basis of Chronic Wounds

Chronic Wounds Clinical Trial

Official title:

Genetic and Epigenetic Basis of Chronic Wounds

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03793062
• Other study ID #: STUDY23080025
• Secondary ID: R01DK135447
• Status: Recruiting
• Start date: December 4, 2018
• Est. completion date: December 31, 2028

Study information

• Verified date: April 2024
• Source: University of Pittsburgh
• Contact: Kiyan Shadmani, MPH
• Phone: 234-380-9436
• Email: kiyanshadmani[@]pitt.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This pilot study is designed for chronic wounds that fail to heal in a timely manner carry specific genetic signatures. These genetic signatures will be studied using debrided wound tissue that is removed by the wound care provider as part of standard of care. The reference genomic signature will be evaluated by obtaining blood samples and will be compared with wound debrided tissue genomic signature to understand wound specific genomic changes.

Description:

Chronic wounds affect a large fraction of the world population and poses major threat to the public health and economy of the United States affecting 6.5 million patients. It has been estimated that approximately 2% of the population residing in developed countries, will experience at least one chronic wound during their lifetime. Current treatment options for chronic wounds are insufficient due to lack of individual specific genetic information. To improve therapy, an increase in the investigator's understanding of the genetic predisposition of individuals which result in impaired wound healing response is warranted. Information about these individual specific genetic and epigenetic regulations can altogether yield subset of repair genes which can serve as master regulators of wound healing. The effect of specific genetic information is also modified a lot by environmental epigenetic factors. Epigenetic changes have been shown to control the wound healing outcomes. In this prospective pilot study, patients with chronic wounds visiting UPMC hospitals will be enrolled. Patients enrolled in the study will be followed for 16 weeks (+ or - 2 weeks). Within this time, debrided wound tissue will be collected, when available, as part of their standard of care at the clinics. The study consists of four study visits (Week 0, Week 4, Week 8 and Week 16 or earlier if target would is healed before that time). Study visit 1 consists of obtaining informed consent, medical history, current medications, and baseline demographics including, but not limited to: age, gender, zip code, ethnicity/race, marital status, education level, employment history, household income, number of household member. Digital imaging along with the collection of a saliva and blood sample will be performed during the visit. Participants will be asked to complete fourteen health questionnaires. Study visits two and three consists of digital imaging, along with a medication and adverse event review. Debridement tissue, if available, will be collected, if not collected earlier, during a follow up standard of care as part of wound care visit during the 16-week period. Study visit 4 (Healing Confirmation visit) consists of digital imaging, medication and adverse event review, along with Transepidermal water loss (TEWL) measurements.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 256
• Est. completion date: December 31, 2028
• Est. primary completion date: June 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• Age = 18 years
• Willing to comply with protocol instructions, including all study visits and study activities.
• Chronic wounds (> than four weeks since onset)
• Clinically diagnosed diabetic or non-diabetic ulcer.
• For patients with multiple wounds, the largest wound will be used for the study.

Exclusion Criteria:

• Individuals who are deemed unable to understand the procedures, risks and benefits of the study,(i.e. unable to provide informed consent)
• Pregnant females (self-declared) or lactating
• Subjects with marked immunodeficiency (HIV/AIDS or immune-suppressive medications)
• Prisoners

Related Conditions & MeSH terms

• Chronic Wounds
• Wounds and Injuries

Intervention

Other:
• No Interventions
Not applicable - No Interventions

Locations

Country	Name	City	State
United States	UPMC Wound Care Centers	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pittsburgh	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (10)

Ai L, Kim WJ, Demircan B, Dyer LM, Bray KJ, Skehan RR, Massoll NA, Brown KD. The transglutaminase 2 gene (TGM2), a potential molecular marker for chemotherapeutic drug sensitivity, is epigenetically silenced in breast cancer. Carcinogenesis. 2008 Mar;29(3):510-8. doi: 10.1093/carcin/bgm280. Epub 2008 Jan 3. — View Citation

Chernov AV, Sounni NE, Remacle AG, Strongin AY. Epigenetic control of the invasion-promoting MT1-MMP/MMP-2/TIMP-2 axis in cancer cells. J Biol Chem. 2009 May 8;284(19):12727-34. doi: 10.1074/jbc.M900273200. Epub 2009 Mar 13. — View Citation

Crovetti G, Martinelli G, Issi M, Barone M, Guizzardi M, Campanati B, Moroni M, Carabelli A. Platelet gel for healing cutaneous chronic wounds. Transfus Apher Sci. 2004 Apr;30(2):145-51. doi: 10.1016/j.transci.2004.01.004. — View Citation

Gottrup F. A specialized wound-healing center concept: importance of a multidisciplinary department structure and surgical treatment facilities in the treatment of chronic wounds. Am J Surg. 2004 May;187(5A):38S-43S. doi: 10.1016/S0002-9610(03)00303-9. — View Citation

Mann J, Oakley F, Akiboye F, Elsharkawy A, Thorne AW, Mann DA. Regulation of myofibroblast transdifferentiation by DNA methylation and MeCP2: implications for wound healing and fibrogenesis. Cell Death Differ. 2007 Feb;14(2):275-85. doi: 10.1038/sj.cdd.4401979. Epub 2006 Jun 9. — View Citation

Rahnama F, Shafiei F, Gluckman PD, Mitchell MD, Lobie PE. Epigenetic regulation of human trophoblastic cell migration and invasion. Endocrinology. 2006 Nov;147(11):5275-83. doi: 10.1210/en.2006-0288. Epub 2006 Aug 3. — View Citation

Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, Gottrup F, Gurtner GC, Longaker MT. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 2009 Nov-Dec;17(6):763-71. doi: 10.1111/j.1524-475X.2009.00543.x. — View Citation

Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med. 1999 Sep 2;341(10):738-46. doi: 10.1056/NEJM199909023411006. No abstract available. — View Citation

Ti D, Li M, Fu X, Han W. Causes and consequences of epigenetic regulation in wound healing. Wound Repair Regen. 2014 May-Jun;22(3):305-12. doi: 10.1111/wrr.12160. — View Citation

Zhang W, Shiraishi A, Suzuki A, Zheng X, Kodama T, Ohashi Y. Expression and distribution of tissue transglutaminase in normal and injured rat cornea. Curr Eye Res. 2004 Jan;28(1):37-45. doi: 10.1076/ceyr.28.1.37.23493. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Epigenetic and transcriptome changes in debrided tissue from chronic wounds in healing vs non healing phase .	The wound area (digital planimetry at d0/ 16 week) will classify wounds as heal-high (final 16 week size <40% of initial visit, d0) or heal-low (>60% of initial d0).	16 weeks or healing whichever comes first
Primary	Wound specific genetic changes using whole genome approaches.	To characterize wound specific genetic changes (e.g., mutations) using whole genome approaches. Genome from blood cells will be used as reference	16 weeks or healing whichever comes first
Primary	Identify specific SEEBIN factors.	To Determine the significance of socio-economic, environmental, behavioral, immunological and nutritional (SEEBIN) factors in modifying chronic wound (CW) tissue genomics in a way that affects healing trajectory.	16 weeks or healing whichever comes first