miR-200b & miR-21 in Diabetic Wounds

NCT02581098 | Completed DMC

• 2 other identifiers: 1807426080GM108014/DK114718
• Study Type: observational
• Target: 98
• Locations: 1 country
• Sites: 4

Brief Summary

This study aims to determine if elevated wound-edge endothelial miR-200b is a barrier to wound healing in diabetic patients and also to determine if ex vivo supplementation of miR-21 mimic and recombinant MFG-E8 resolve inflammation in wound macrophages isolated from NPWT sponges from diabetic wounds. This study will enroll 124 (60 in the miR-200b arm and 64 in the miR21 arm) Diabetic Wound patients who have wound tissue oxygenation adequate to support wound healing and will be in the study for 14 weeks that includes 4 study visits.

Conditions

Diabetes Mellitus; Foot Ulcer; Ulcer; Diabetic Foot Ulcer; Wound; Wound Heal

Outcome Measures

Primary Outcomes (2)

• Wound-edge endothelial miR-200b

  This study aims to determine if elevated wound-edge endothelial miR-200b and attenuated wound macrophage miR-21 levels are barriers to wound healing (closure) in diabetic wounds.

  14 weeks

• Wound macrophage isolation to determine miR-21

  To determine if ex vivo supplementation of miR-21 mimic and recombinant MFG-E8 resolve inflammation in wound macrophages isolated from Negative Pressure Wound Therapy sponges from diabetic wounds.

  14 weeks

Interventions

No interventions OTHER

No interventions

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

124 subjects with diabetic foot ulcers who have wound tissue oxygenation adequate to support wound healing

You may qualify if:

• Ages 18 and older
• Willing and able to provide informed consent
• Willing and able to comply with protocol instructions, including all biopsies and study visits
• Diabetes Mellitus
• Chronic wounds (open \>30d) of any etiology
• Subjects with Negative Pressure Wound Therapy (NPWT or also called a wound vac) (Note: Applies only to the miR-21 arm)

You may not qualify if:

• Revascularization surgery on the target wound within 60 days prior to enrollment
• Inadequate arterial supply, as evidenced by any of the following:
• Transcutaneous Oxygen Measurement (TcOM) \< 30mmg
• Ankle Brachial Index (ABI) \<0.7 or 1.3
• Toe Brachial Index (TBI) \<0.6
• Subjects with marked immunodeficiency (HIV/AIDS, organ transplant patients and actively being treated for cancer)
• Trauma wounds
• Wounds closed or to be closed by flap or graft coverage
• Women who are pregnant

Sponsors & Collaborators

• Indiana University: lead
• National Institutes of Health (NIH): collaborator

Study Sites (4)

IU Health Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

OSU Hospital East

Columbus, Ohio, 43205, United States

Location

Davis Heart and Lung Research Institute

Columbus, Ohio, 43210, United States

Location

Martha Morehouse Medical Plaza

Columbus, Ohio, 43221, United States

Location

Related Publications (14)

• Chan YC, Khanna S, Roy S, Sen CK. miR-200b targets Ets-1 and is down-regulated by hypoxia to induce angiogenic response of endothelial cells. J Biol Chem. 2011 Jan 21;286(3):2047-56. doi: 10.1074/jbc.M110.158790. Epub 2010 Nov 16.

  PMID: 21081489 BACKGROUND

• Chan YC, Roy S, Khanna S, Sen CK. Downregulation of endothelial microRNA-200b supports cutaneous wound angiogenesis by desilencing GATA binding protein 2 and vascular endothelial growth factor receptor 2. Arterioscler Thromb Vasc Biol. 2012 Jun;32(6):1372-82. doi: 10.1161/ATVBAHA.112.248583. Epub 2012 Apr 12.

  PMID: 22499991 BACKGROUND

• Chin D, Boyle GM, Theile DR, Parsons PG, Coman WB. The human genome and gene expression profiling. J Plast Reconstr Aesthet Surg. 2006;59(9):902-11. doi: 10.1016/j.bjps.2006.01.008. Epub 2006 Mar 9.

  PMID: 16920579 BACKGROUND

• Gardner SE, Frantz RA, Doebbeling BN. The validity of the clinical signs and symptoms used to identify localized chronic wound infection. Wound Repair Regen. 2001 May-Jun;9(3):178-86. doi: 10.1046/j.1524-475x.2001.00178.x.

  PMID: 11472613 BACKGROUND

• Parsek MR, Singh PK. Bacterial biofilms: an emerging link to disease pathogenesis. Annu Rev Microbiol. 2003;57:677-701. doi: 10.1146/annurev.micro.57.030502.090720.

  PMID: 14527295 BACKGROUND

• Roy S, Khanna S, Rink C, Biswas S, Sen CK. Characterization of the acute temporal changes in excisional murine cutaneous wound inflammation by screening of the wound-edge transcriptome. Physiol Genomics. 2008 Jul 15;34(2):162-84. doi: 10.1152/physiolgenomics.00045.2008. Epub 2008 May 6.

  PMID: 18460641 BACKGROUND

• Roy S, Patel D, Khanna S, Gordillo GM, Biswas S, Friedman A, Sen CK. Transcriptome-wide analysis of blood vessels laser captured from human skin and chronic wound-edge tissue. Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14472-7. doi: 10.1073/pnas.0706793104. Epub 2007 Aug 29.

  PMID: 17728400 BACKGROUND

• Schafer M, Werner S. Transcriptional control of wound repair. Annu Rev Cell Dev Biol. 2007;23:69-92. doi: 10.1146/annurev.cellbio.23.090506.123609.

  PMID: 17474876 BACKGROUND

• 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.

  PMID: 19903300 BACKGROUND

• Shilo S, Roy S, Khanna S, Sen CK. Evidence for the involvement of miRNA in redox regulated angiogenic response of human microvascular endothelial cells. Arterioscler Thromb Vasc Biol. 2008 Mar;28(3):471-7. doi: 10.1161/ATVBAHA.107.160655. Epub 2008 Feb 7.

  PMID: 18258815 BACKGROUND

• Shilo S, Roy S, Khanna S, Sen CK. MicroRNA in cutaneous wound healing: a new paradigm. DNA Cell Biol. 2007 Apr;26(4):227-37. doi: 10.1089/dna.2006.0568.

  PMID: 17465889 BACKGROUND

• Hopf HW, Ueno C, Aslam R, Burnand K, Fife C, Grant L, Holloway A, Iafrati MD, Mani R, Misare B, Rosen N, Shapshak D, Benjamin Slade J Jr, West J, Barbul A. Guidelines for the treatment of arterial insufficiency ulcers. Wound Repair Regen. 2006 Nov-Dec;14(6):693-710. doi: 10.1111/j.1524-475X.2006.00177.x. No abstract available.

  PMID: 17199834 BACKGROUND

• Padberg FT, Back TL, Thompson PN, Hobson RW 2nd. Transcutaneous oxygen (TcPO2) estimates probability of healing in the ischemic extremity. J Surg Res. 1996 Feb 1;60(2):365-9. doi: 10.1006/jsre.1996.0059.

  PMID: 8598670 BACKGROUND

• Wutschert R, Bounameaux H. Determination of amputation level in ischemic limbs. Reappraisal of the measurement of TcPo2. Diabetes Care. 1997 Aug;20(8):1315-8. doi: 10.2337/diacare.20.8.1315.

  PMID: 9250461 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Tissue, wound fluid

MeSH Terms

Conditions

Diabetes Mellitus; Foot Ulcer; Ulcer; Diabetic Foot; Wounds and Injuries

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Foot Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Leg Ulcer; Skin Ulcer; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetic Neuropathies

Study Officials

• Chandan K Sen, PhD

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 13, 2015
• First Posted: October 20, 2015
• Study Start: August 1, 2015
• Primary Completion: June 26, 2023
• Study Completion: June 26, 2023
• Last Updated: April 25, 2024

Record last verified: 2024-04

Locations

US (4)