Phase I trial to evaluate the safety of H5.020CMV.PDGF-b and limb compression bandage for the treatment of venous leg ulcer: Trial A

Human Gene Therapy

Volumn 15, Issue 10, 2004, Pages 1003-1019

  Margolis, David J ^a   Cromblehome, Timothy ^b   Herlyn, Meenhard ^c   Cross, Philip ^d   Weinberg, Linda ^a   Filip, Jennifer ^a   Propert, Kathleen ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

^c WISTAR INSTITUTE   (United States)

^d Philip J Cross and Associates   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOVIRUS VECTOR; PLATELET DERIVED GROWTH FACTOR BB; PLATELET DERIVED GROWTH FACTOR; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PLATELET-DERIVED GROWTH FACTOR BB;

CLINICAL PROTOCOL; CLINICAL RESEARCH; DOSE CALCULATION; GENE OVEREXPRESSION; GENE THERAPY; HUMAN; LEG COMPRESSION; LEG ULCER; PATIENT SELECTION; PHASE 1 CLINICAL TRIAL; REVIEW; TREATMENT PLANNING; ADENOVIRUS; ANIMAL; ARTICLE; BANDAGE; CLINICAL TRIAL; GENE VECTOR; GENETICS; INFLAMMATION; LEG; METABOLISM; METHODOLOGY; PATHOLOGY; PRESSURE; PROSPECTIVE STUDY; RABBIT; VARICOSIS; WOUND HEALING;

ADENOVIRIDAE; ANIMALIA;

ADENOVIRIDAE; ANIMALS; BANDAGES; CLINICAL TRIALS; GENE THERAPY; GENETIC VECTORS; HUMANS; INFLAMMATION; LEG; LEG ULCER; PLATELET-DERIVED GROWTH FACTOR; PRESSURE; PROSPECTIVE STUDIES; RABBITS; RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA; VARICOSE ULCER; WOUND HEALING;

EID: 5644288449     PISSN: 10430342     EISSN: None     Source Type: Journal    
DOI: 10.1089/hum.2004.15.1003     Document Type: Review

References (70)

1. Lazarus GS, Cooper DM, Knighton DR, Margolis DJ, Pecoraro RE, Rodeheaver G, et al Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol 1994;130:489-493.
2. Woodall RD. Tissue viability-living with leg ulcers: A patient's personal experience. Nurs Stand 1996;10:52.
3. Kaplan RM, Criqui MH, Denenberg JO, Bergan J, Fronek A. Quality of life in patients with chronic venous disease: San Diego population study. J Vasc Surg 2003;37:1047-1053.
4. Franks PJ, Moffatt CJ, Connelly M, Bosanquet N, Oldroyd M, Greenhalgh RM, et al. Community leg ulcer clinics: Effect on quality of life. Phlebology 1994;9:83-86.
5. Phillips T, Stanton B, Provan A, Lew R. A study of the impact of leg ulcers on quality of life: Financial, social, and psychologic implications. J Am Acad Dermatol 1994;31:49-53.
6. Coon WW, Willis PW3, Keller JB. Venous thromboembolism and other venous disease in the Tecumseh community health study. Circulation 1973;48:839-846.
7. Hallbook T. Leg ulcer epidemiology. Acta Chir Scand 1988;544:17-20.
8. Margolis DJ, Bilker W, Santanna J, Baumgarten M. Venous leg ulcer: Incidence and prevalence in the elderly. J Am Acad Dermatol 2002;46:381-386.
9. Callam MJ, Harper DR, Dale JJ, Ruckley CV. Chronic ulcer of the leg: Clinical history. BMJ 1987;294:1389-1391.
10. Phillips TJ. Chronic cutaneous ulcers: Etiology and epidemiology. J Invest Dermatol 1994;102:38S-41S.
11. Lees TA, Lambert D. Prevalence of lower limb ulceration in an urban health district. Br J Surg 1992;79:1032-1034.
12. Mostow EN. Diagnosis and classification of chronic wounds. Clin Dermatol 1994;12:3-11.
13. Baker SR, Stacey MC, Singh G, Hoskin SE, Thompson PJ. Aetiology of chronic leg ulcers. Eur J Vasc Surg 1992;6:245-251.
14. Falanga V, Kirsner R, Katz MH, Gould E, Eaglstein WH, McFalls S. Pericapillary fibrin cuffs in venous ulceration: Persistence with treatment and during ulcer healing. J Dermatol Surg Oncol 1993;18:409-414.
15. Weingarten MS. State-of-the-art treatment of chronic venous disease. Clin Infect Dis 2001;32:949-954.
16. Criqui MH, Jamosmos M, Fronek A, Denenberg JO, Langer RD, Bergan J, et al. Chronic venous disease in an ethnically diverse population: The San Diego population study. Am J Epidemiol 2003;158:448-456.
17. Balslev E, Thomsen HK, Danielsen L, Warburg F. The occurrence of pericapillary fibrin in venous hypertension and ischaemic leg ulcers: A histopathological study. Br J Dermatol 1992;126:582-585.
18. Scott HJ, McMullin GM, Coleridge-Smith PD, Scurr JH. Venous disease: Investigation and treatment, fact or fiction? Ann R Coll Surg Engl 1990;72:188-192.
19. Falanga V, Eaglstein WH. The trap hypothesis of venous ulceration. Lancet 1993;341:1006-1008.
20. Margolis DJ, Cohen JH. Management of chronic venous leg ulcers: A literature-guided approach. Clin Dermatol 1994;12:19-26.
21. Stromberg K, Chapekar MS, Goldman BA, Cavagnaro JA. Regulatory concerns in the development of topical recombinant ophthalmic and cutaneous wound healing biologics. Wound Repair Regen 1994;2:155-164.
22. Nelzen O, Bergqvist D, Lindhagen A, Hallbook T. Chronic leg ulcers: An underestimated problem in primary health care among elderly patients. J Epidemiol Community Health 1991;45:184-187.
23. Scholz A. Historical aspects. In: Westerhof W, editor. Leg Ulcers: Diagnosis and Treatment. Amsterdam: Elsevier, 1993, pp. 5-18.
24. Fletcher A, Cullum F, Sheldon TA. A systematic review of compression treatment for venous leg ulcers. BMJ 1997;315:576-580.
25. Kantor J, Margolis DJ. Venous Leg Ulcers. In: Williams H, Bigby M, Diepgen T, Herxheimer A, Naldi L, Rzany B, editors. Evidence-Based Dermatology. London: BMJ Publishing Group, 2003, pp. 591-602.
26. Skene AJ, Smith JM, Dore CJ, Charlett A, Lewis JD. Venous leg ulcers: A prognostic index to predict time to healing. BMJ 1992;305:1119-1121.
27. Stiller MJ, Pak GH, Shupack JL, Thaler S, Kenney C, Jondreau L. A portable pulsed electromagnetic field (PEMF) device to enhance healing of recalcitrant venous ulcers: A double-blind, placebo-controlled clinical trial. Br J Dermatol 1992;127:147-154.
28. Kantor J, Margolis DJ. Expected healing rates for chronic wounds. Wounds 2000;12:155-158.
29. Margolis DJ, Berlin JA, Strom BL. Which venous leg ulcers will heal with a limb compression bandage? Am J Med 2000;109:15-19.
30. Clark RAF. Cutaneous tissue repair: Basic biologic considerations. J Am Acad Dermatol 1985;13:701-725.
31. Clark RAF. Wound repair: Overview and general considerations. In: Clark RAF, editor. The Molecular and Cellular Biology of Wound Repair. New York: Plenum, 1996, pp. 3-50.
32. Martin P. Wound healing: Aiming for perfect skin regeneration. Science 1997;276:75-81.
33. Pierce GF, Tarpley JE, Tseng J, Bready J, Chang D, Kenney WC, et al. Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds. J Clin Invest 1995;96:1336-1350.
34. Pierce GF, Mustoe TA. Pharmacologic enhancement of wound healing. Annu Rev Med 1995;46:467-481.
35. Beer HD, Longaker MT, Werner S. Reduced expression of PDGF and PDGF receptors during impaired wound healing. J Invest Dermatol 1997;109:132-138.
36. Pierce GF, Mustoe TA, Lingelbach J, Masakowski VR, Gramates P, Deuel TF. Transforming growth factor β reverses the glucocorticoid-induced wound-healing deficit in rats: Possible regulation in macrophages by platelet-derived growth factor. Proc Natl Acad Sci USA 1989;86:2229-2233.
37. Levenson SM, Geever EF, Crowley LV, Gates JF, Berard CW, Rosen H. The healing of rat skin wounds. Ann Surg 1965;161:293-308.
38. Danilenko DM, Ring BD, Tarpley JE, Morris B, Van GY, Morawiecki A, et al. Growth factors in porcine full and partial thickness burn repair: Differing targets and effects of keratinocyte growth factor, platelet-derived growth factor-BB, epidermal growth factor, and Neu differentiation factor. Am J Pathol 1995;147:1261-1277.
39. Gross EA, Wood CR, Lazarus GS, Margolis DJ. Venous leg ulcers: An analysis of underlying disease. Br J Dermatol 1993;129:270-274.
40. Margolis DJ. The treatment of lower extremity venous ulceration. Hosp Pract 1992;27:32-44.
41. Falanga V, Eaglstein WH. A therapeutic approach to venous ulcers. J Am Acad Dermatol 1986;14:777-784.
42. Steed DL, Goslen JB, Holloway GA, Malone JM, Bunt TJ, Webster MW. Randomized prospective double-blinded trial in healing chronic foot ulcers. Diabetes Care 1992;15:1598-1604.
43. Falanga V, Eaglstein WH, Bucalo B, Katz MH, Harris B, Carson P. Topical use of human recombinant epidermal growth factor (h-EGF) in venous ulcers. J Dermatol Surg Oncol 1992;18:604-606.
44. Kirsner RS, Falanga V, Eaglstein WH. The biology of skin grafts: Skin grafts as pharmacologic agents. Arch Dermatol 1993;129:481-483.
45. Falanga V, Margolis D, Alvarez O, Auletta M, Maggiacomo, Altman M, et al. Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent. Human Skin Equivalent Investigators Group. Arch Dermatol 1998;134:293-300.
46. Bennett SP, Griffiths GD, Schor AM, Leese GP, Schor SL. Growth factors in the treatment of diabetic foot ulcers. Br J Surg 2003;90:133-146.
47. Kozarsky KF, Wilson JM. Gene therapy: Adenovirus vectors. Curr Opin Genet Dev 1993;3:499-503.
48. Yao F, Eriksson E. Gene therapy in wound repair and regeneration. Wound Repair Regen 2000;8:443-451.
49. Lindblad WJ. Gene therapy in wound healing-2000: A promising future. Wound Repair Regen 2000;8:441-442.
50. Margolis DJ, Crombleholme T, Herlyn M. Clinical protocol: Phase I trial to evaluate the safety of H5.020CMV.PDGF-B for the treatment of a diabetic insensate foot ulcer. Wound Repair Regen 2000;8:480-493.
51. Crombleholme TM. Adenoviral-mediated gene transfer in wound healing. Wound Repair Regen 2000;8:460-472.
52. Chandler LA, Gu DL, Ma C, Gonzalez AM, Doukas J, Nguyen T, et al. Matrix-enabled gene transfer for cutaneous wound repair. Wound Repair Regen 2000;8:473-479.
53. Khavari PA, Rollman O, Vahlquist A. Cutaneous gene transfer for skin and systemic diseases. J Intern Med 2002;252:1-10.
54. Mulligan RC. The basic science of gene therapy. Science 1993;260:929-932.
55. Crystal RG. Transfer of genes to humans: Early lessons and obstacles to success. Science 1995;270:404-410.
56. Kovesdi I, Brough DE, Bruder JT, Wickham TJ. Adenoviral vectors for gene transfer. Curr Opin Biotechnol 1997;8:583-589.
57. Lee MG, Kremer EJ, Perricaudet M. Adenoviral vectors. Mol Cell Biol Hum Dis Ser 1995;5:20-32.
58. Bett AJ, Prevec L, Graham FL. Packaging capacity and stability of human adenovirus type 5 vectors. J Virol 1993;67:5911-5921.
59. Harvey BG, Hackett NR, El Sawy T, Rosengart TK, Hirschowitz EA, Lieberman MD, et al. Variability of human systemic humoral immune responses to adenovirus gene transfer vectors administered to different organs. J Virol 1999;73:6729-6742.
60. Margolis DJ, Berlin JA, Strom BL. Risk factors associated with the failure of a venous leg ulcer to heal. Arch Dermatol 1999;135:920-926.
61. Liechty KW, Nesbit M, Herlyn M, Radu A, Adzick NS, Crombleholme TM. Adenoviral-mediated overexpression of platelet-derived growth factor-B corrects ischemic impaired wound healing. J Invest Dermatol 1999;113:375-383.
62. Sylvester KG, Nesbit M, Radu A, Herlyn M, Adzick NS, Crombleholme TM. Adenoviral-mediated gene transfer in wound healing: Acute inflammatory response in human skin in the SCID mouse model. Wound Repair Regen 2000;8:36-44.
63. Liechty KW, Sablich TJ, Adzick NS, Crombleholme TM. Recombinant adenoviral mediated gene transfer in ischemic impaired wound healing. Wound Repair Regen 1999;7:148-153.
64. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). E9 Statistical Principles for Clinical Trials. Available at http://www.fda.gov/cder/guidance/ICH_E9-fnl.PDF (accessed August 2004).
65. Gelfand JM, Hofstad O, Margolis DJ. Surrogate end points for treatment of venous leg ulcers. J Invest Dermatol 2002;119:1420-1425.
66. Tallman P, Muscare E, Carson P, Eaglstein WH, Falanga V. Initial rate of healing predicts complete healing of venous ulcers. Arch Dermatol 1997;133:1231-1234.
67. Weingarten MS, Czeredarczuk M, Scovell S, Branas CC, Mignogna GM, Wolferth CC, Jr. A correlation of air plethysmography and color-flow-assisted duplex scanning in the quantification of chronic venous insufficiency. J Vasc Surg 1996;24:750-754.
68. Campbell WB, Halim AS, Aertssen A, Ridler BM, Thompson JF, Niblett PG. The place of duplex scanning for varicose veins and common venous problems. Ann R Coll Surg Engl 1996;78:490-493.
69. Max MB, Lynch SA, Muir J, Shoaf SE, Smoller B, Dubner R. Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy. N Engl J Med 1992;326:1250-1256.
70. Herrick SE, Sloan P, McGurk M, Freak L, McCollum CN, Ferguson MW. Sequential changes in histologic pattern and extracellular matrix deposition during the healing of chronic venous ulcers. Am J Pathol 1992;141:1085-1095.