Adipose-Derived Stromal Cells (ASC's) for Pressure Ulcers

Official title

A Pilot Study: Evaluating the Safety and Feasibility of Using Autologous Adipose-Derived Stromal Cells From Stromal Vascular Fraction (SVF) on Adults With Pressure Ulcers or Diabetic Foot Ulcers

Overview

This pilot study of 12 patients will test the safety and efficacy of applying autologous, adipose-derived stromal cells (ASCs), uncultured, on a Stage III or IV pressure ulcer or diabetic foot ulcers. Patients will undergo a minimal risk liposuction procedure to withdraw 50-100 cc of adipose tissue. The tissue would be processed to extract the stromal layer of cells that contain stem cells. The ASCs would be injected into a fibrin sealant to be applied to the wound. Patients would be followed for 6 weeks to assess wound healing and tolerance of the treatment.

Detailed description

Wound healing for Stage III and IV pressure ulcers or diabetic foot ulcers can take four to six weeks or longer and cost upwards of $40,000 to treat. Past studies have shown that adipose tissue contains progenitor cells or regenerative cells that can release multiple angiogenic growth factors and cytokines including vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and chemokine stromal cell-derived factor-1 (SDF-1). A current literature review revealed that there is research related to use of stem cells to enhance wound healing, in particular with ischemic or radiation-induced ulcers. However, there is limited research completed on use of stem cells or ASCs with pressure ulcers. The goal is to heal pressure ulcers faster and prevent further complications using the patient's own natural ASCs.

Interventions

• Biological Adipose-derived stromal cells
  Adipose-derived stromal cells contain stem cells which have been successful in enhancing wound healing. The product used as the carrier is a fibrin sealant called TISSEEL. Pre-pilot testing was done to verify viability of the stromal cells for up to 72 hours in the fibrin sealant.
• Drug Adipose-derived stromal cells

Primary outcome measures

• Free of wound infection [Time frame: one week]

Secondary outcome measures (2)

• Liposuction procedure without complication [Time frame: one week]
• Improved wound healing [Time frame: weekly observation for 6 weeks]

Eligibility criteria

Inclusion criteria

• Males and females
• Stage III pressure ulcers measuring 5 cc - 36 cc in volume (as measured by filling the wound with Normal Saline).
• Inpatient or outpatient treatment of pressure ulcers
• Diabetic Foot Ulcer Stage 1 or 2 of any size
• Co-morbidities may include:

• Peripheral Vascular Disease (PVD)
• Coronary Artery Disease (CAD)
• Chronic Renal Disease (CRD)
• Chronic Liver Disease (CLD)
• Hypertension (HTN)
• Diabetes
• The ability of subjects to give appropriate consent or have an appropriate representative available to do so
• The ability of subjects to return for weekly wound assessments

Exclusion criteria

• Patients with allergies to TISSEEL, Tegaderm, or silicon
• Diabetics with poor glucose metabolic control (HbA1c > 9)
• Target wounds that are in close proximity to potential cancerous lesions
• Patients who require Negative Pressure Wound Therapy (NPWT), limb amputation, or surgical intervention at the target wound at the time of screening
• Wounds located on the face
• Patients with Stage 5 or 6 Peripheral Vascular disease (specifically, wounds that are caused by peripheral vascular disease such as leg ulcers)
• Wounds caused by diabetes mellitus (diabetic foot ulcers).
• BMI of <16 Clinical signs of critical colonization or local infection
• Prolonged (> 6 months) use of steroids
• Patients on active regimen of chemotherapy
• Patients receiving radiation in proximity of wound
• Decompensated chronic liver disease

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Mayo Clinic in Florida — Jacksonville

Publications

• Lu D, Chen B, Liang Z, Deng W, Jiang Y, Li S, Xu J, Wu Q, Zhang Z, Xie B, Chen S. Comparison of bone marrow mesenchymal stem cells with bone marrow-derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: a double-blind, randomized, controlled trial. Diabetes Res Clin Pract. 2011 Apr;92(1):26-36. doi: 10.1016/j.diabres.2010.12.010. Epub 2011 Jan 8. PMID 21216483
• Bura A, Planat-Benard V, Bourin P, Silvestre JS, Gross F, Grolleau JL, Saint-Lebese B, Peyrafitte JA, Fleury S, Gadelorge M, Taurand M, Dupuis-Coronas S, Leobon B, Casteilla L. Phase I trial: the use of autologous cultured adipose-derived stroma/stem cells to treat patients with non-revascularizable critical limb ischemia. Cytotherapy. 2014 Feb;16(2):245-57. doi: 10.1016/j.jcyt.2013.11.011. PMID 24438903
• Rigotti G, Marchi A, Galie M, Baroni G, Benati D, Krampera M, Pasini A, Sbarbati A. Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process mediated by adipose-derived adult stem cells. Plast Reconstr Surg. 2007 Apr 15;119(5):1409-1422. doi: 10.1097/01.prs.0000256047.47909.71. PMID 17415234
• Akita S, Yoshimoto H, Akino K, Ohtsuru A, Hayashida K, Hirano A, Suzuki K, Yamashita S. Early experiences with stem cells in treating chronic wounds. Clin Plast Surg. 2012 Jul;39(3):281-92. doi: 10.1016/j.cps.2012.04.005. Epub 2012 May 22. PMID 22732376
• Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, Redl H, Rubin JP, Yoshimura K, Gimble JM. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cy PMID 23570660
• Falanga V, Iwamoto S, Chartier M, Yufit T, Butmarc J, Kouttab N, Shrayer D, Carson P. Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds. Tissue Eng. 2007 Jun;13(6):1299-312. doi: 10.1089/ten.2006.0278. PMID 17518741
• Gorecki C, Brown JM, Nelson EA, Briggs M, Schoonhoven L, Dealey C, Defloor T, Nixon J; European Quality of Life Pressure Ulcer Project group. Impact of pressure ulcers on quality of life in older patients: a systematic review. J Am Geriatr Soc. 2009 Jul;57(7):1175-83. doi: 10.1111/j.1532-5415.2009.02307.x. Epub 2009 May 21. PMID 19486198
• Graves N, Birrell F, Whitby M. Effect of pressure ulcers on length of hospital stay. Infect Control Hosp Epidemiol. 2005 Mar;26(3):293-7. doi: 10.1086/502542. PMID 15796283

Identifiers

NCT: NCT02375802 · 14-002855

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗