Effect of Topical Basic Fibroblast Growth Factor on the Healing of Chronic Diabetic Neuropathic Ulcer of the foot: A pilot, randomized, double-blind, placebo-controlled study

Richard, Jean-Louis; Parer-Richard, C.; Daurès, Jean‐Pierre; Clouet, Sophie; Vannereau, D.; Bringer, J.; Rodier, M.; Jacob, Claudine; Comte-Bardonnet, Martine

doi:10.2337/diacare.18.1.64

Cited by 209 publications

(165 citation statements)

References 18 publications

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“…The reported diabetic ulcer healing rates ranged from 33 to 57.5% at a cutoff time of 12-20 weeks, when the growth factors PDGF or FGF were used in controlled trials (17,18). In a small pilot randomized double-blind study reported by Richard et al (18), nine chronic neuropathic plantar foot ulcers (Wegner grade I-III) were treated with topical FGF for a total of 18 weeks.…”

Section: Hegf and Diabetic Foot Ulcersmentioning

confidence: 99%

Human Epidermal Growth Factor Enhances Healing of Diabetic Foot Ulcers

et al. 2003

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OBJECTIVE -To study the healing effect of recombinant human epidermal growth factor (hEGF) on diabetic foot ulcers. RESEARCH DESIGN AND METHODS-A total of 127 consecutive patients were screened and 61 diabetic subjects were recruited into this double-blind randomized controlled study. Predetermined criteria were used for diagnosis and classification of the diabetic wound. The patients were randomized into three groups. All patients attended our Diabetes Ambulatory Care Center every other week for joint consultation with the diabetologist and the podiatrist. Group 1 (control) was treated with Actovegin 5% cream (Actovegin), group 2 with Actovegin plus 0.02% (wt/wt) hEGF, and group 3 with Actovegin plus 0.04% (wt/wt) hEGF. The study end point was the complete closure of the wound. Failure to heal was arbitrarily defined as incomplete healing after 12 weeks.RESULTS -Final data were obtained from 61 patients randomly assigned into three groups. The mean ages of the patients, wound sizes, wound duration, metabolic measurements, and comorbidities were comparable within groups, except that group 3 had more female patients. Mean follow-up for the patients was 24 weeks. Data were cutoff at 12 weeks, and results were analyzed by intention to treat. After 12 weeks, in group 1 (control) eight patients had complete healing, two patients underwent toe amputation, and nine had nonhealing ulcers. In group 2 (0.02% [wt/wt] hEGF) 12 patients experienced wound healing, 2 had toe amputations, and 7 had nonhealing ulcers. Some 20 of 21 patients in group 3 (0.04% [wt/wt] hEGF) showed complete wound healing. Healing rates were 42.10, 57.14, and 95% for the control, 0.02% (wt/wt) hEGF, and 0.04% (wt/wt) hEGF groups, respectively. Kaplan-Meier survival analysis suggested that application of cream with 0.04% (wt/wt) hEGF caused more ulcers to heal by 12 weeks and increased the rate of healing compared with the other treatments (log-rank test, P ϭ 0.0003).CONCLUSIONS -Our data support the contention that application of hEGF-containing cream, in addition to good foot care from a multidisciplinary team, significantly enhances diabetic foot ulcer wound healing and reduces the healing time. Diabetes Care 26:1856 -1861, 2003D iabetic foot ulcer is a major complication of diabetes. People with diabetes show a 5-to 50-fold higher risk of nontraumatic amputation compared with individuals who do not suffer from diabetes (1). Between 1996 and 1998, diabetic patients accounted for 47% of all the lower-limb amputations performed in our hospital (M.W.T., K.-M.L., G.K., unpublished data), comparable to published data (2). The major risk factor leading to diabetic foot ulcer is poor diabetes control, which results in neuropathic and vascular changes. In general, diabetic foot ulcers are difficult to heal and frequently lead to amputation if complicated by infection and gangrene. Several new treatment modalities, such as exposure to an oxygen chamber, the use of platelet-derived growth factor (PDGF), and the application of various local dressings, have p...

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Section: Hegf and Diabetic Foot Ulcersmentioning

confidence: 99%

Human Epidermal Growth Factor Enhances Healing of Diabetic Foot Ulcers

et al. 2003

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“…Only a few well-controlled, randomized clinical trials have assessed the usefulness of growth factors in healing chronic ulcers, and the results have been largely discrepant. The use of recombinant PDGF was shown to improve diabetic ulcer healing, healing rates, and ulcer size, 101 and to improve healing rates in pressure ulcers, 102,103 but the use of recombinant FGF was not effective for diabetic ulcers, 104 nor was recombinant EGF effective for venous ulcers. 105 Although no side effects were attributed to the use of growth factors, none of the studies examined costs relative to those of more conservative therapy.…”

Section: Drug Therapymentioning

confidence: 99%

Chronic Venous Insufficiency and Venous Ulceration

Alguire

Mathes

1997

J Gen Intern Med

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OBJECTIVE:To review and summarize the literature on the normal venous circulation of the leg, and the epidemiology, pathophysiology, and treatment of chronic venous insufficiency (CVI).DATA SOURCES: English-language articles identified through a MEDLINE search using the terms venous insufficiency or varicose ulcer and epidemiology, pathophysiology, diagnosis, and clinical trial (pt), and selected cross-references. STUDY SELECTION:Articles on epidemiology, pathophysiology, and treatment of CVI. Randomized, controlled studies were specifically sought for treatment efficacy. DATA EXTRACTION:Data were manually extracted from selected studies and reviews; emphasis was placed on information relevant to the general internist. pproximately 5 million people in the United States exhibit some evidence of chronic venous insufficiency (CVI) and between 400,000 and 500,000 of these individuals have or will develop a venous leg ulcer. 1-3 The signs of CVI include engorgement of the cutaneous veins and dependent edema in mildly affected patients to pigmentation, dermatitis, and ulceration in the more severe cases. Although most patients are asymptomatic, others have leg heaviness and aching or recurrent and recalcitrant leg ulcers punctuated by bouts of cellulitis. These more severe cases are associated with recurrent hospitalization, high health-care costs, and disability. 4,5 Venous insufficiency with trophic skin changes or ulceration is a frustrating problem, which many physicians approach with a sense of ennui. This may be due to the chronic and remitting nature of the problem, the need for lifestyle modification, inconvenient therapies, and contradictory information regarding medical and surgical management. Nevertheless, CVI, including ulceration, is a manageable problem. The purpose of this review is to present the normal anatomy and physiology of the venous circulation and to summarize the epidemiology, pathophysiology, and treatment of CVI. DATA SYNTHESIS: METHODSA MEDLINE search for relevant English-language articles published between 1966 and 1996 was completed using the following MeSH terms: venous insufficiency or varicose ulcer and epidemiology, pathophysiology, diagnosis, and clinical trial (pt). When selecting articles on treatment, randomized, controlled trials were reviewed whenever possible. Emphasis was placed on reviewing articles with clinical relevance for internal medicine physicians. ANATOMY AND NORMAL PHYSIOLOGYVenous blood from the skin and subcutaneous fat is collected in a system of superficial venules and veins that drain toward the deep venous system underneath the fascia via three major pathways: (1) through the long or short saphenous veins, which join the deep system at the saphenofemoral and saphenopopliteal junctions; (2) through the perforating veins originating from the long or short saphenous veins or their branches; or (3) directly into the deep venous system or bypass the deep system entirely and enter the pelvis. 6 Deep veins are categorized as either intramuscular or intermuscular; o...

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“…Investigation of skin transplants has shown that the survival rate of an implant after administration of bFGF rises, due to an increase in revascularization (Burges 1989). In animal models with diminished wound healing (mice with diabetes, with obesity, or in receipt of steroid treatment), bFGF increased the rate of wound healing (Richard et al 1995). Likewise, local application of bFGF in patients with diabetic ulcer led to an increase in healing rates (Albertson et al 1993, Okumura et al 1996.…”

mentioning

confidence: 99%

“…Clinical and animal experiments have shown that local application of growth factors may accelerate this restoration of vascularization/perfusion and lead to improvement of wound and fracture healing (Mustoe et al 1987, Sprugel et al 1987, Rifkin andMoscatelli 1989, Klingbeil et al 1991, Yasko et al 1992, Albertson et al 1993, Lind et al 1993, Kawaguchi et al 1994, Nash et al 1994, Nielsen et al 1994, Steenfos et al 1994, Heckman et al 1995, Nagai et al 1995, Richard et al 1995, Okumura et al 1996, Wang and Aspenberg 1996, Beer et al 1997, Davidson et al 1997, Leunig et al 1997, Bostrom and Camacho 1998, Kato et al 1998, McGee et al 1998, Wieman et al 1998, Corral et al 1999, Radomsky et al 1999, Bouxein et al 2001, Govender et al 2002, Luppen et al 2002, Einhorn et al 2003, Hom and Manivel 2003.…”

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confidence: 99%

Local application of basic fibroblast growth factor increases the risk of local infection after trauma: An in-vitro and in-vivo study in rats

et al. 2007

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Introduction Local application of growth factors to stimulate wound and fracture healing is attracting increasing interest. We studied the effect of local application of a potent angiogenic growth factor, basic fibroblast growth factor (bFGF), on resistance to local infection after soft tissue trauma.Methods For in-vitro and in-vivo experiments, we used recombinant human bFGF. The in-vitro investigations were performed by isolation of human leukocyte fractions, cytokine analysis, phagocytosis assay, flow cytometry, and LDH assay. For the in-vivo investigation, a paired comparison of infection rates was carried out on Sprague-Dawley rats after standardized, closed soft tissue trauma and local, percutaneous bacterial inoculation of different concentrations of Staphylococcus aureus (2 × 10 4 to 2 × 10 7 colony-forming units (cfu)). The lower leg was treated with 1, 10 or 100 ng bFGF (16 animals for each concentration) and without bFGF (16 animals).Results Cytotoxic reactions due to the concentrations of bFGF used could be excluded in the in-vitro tests since incubations of isolated peripheral blood mononuclear cells (PBMCs) with increasing concentrations of bFGF for 24 h did not lead to an increase in the release of lactate dehydrogenase in the culture supernatants compared to corresponding control incubations without any bFGF added. A significant increase in cytokine release was observed after the co-incubation of PBMCs with 100 or 200 ng of the same bFGF that was used for the animal experiments. Furthermore, the capacity of

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Effect of Topical Basic Fibroblast Growth Factor on the Healing of Chronic Diabetic Neuropathic Ulcer of the foot: A pilot, randomized, double-blind, placebo-controlled study

Cited by 209 publications

References 18 publications

Human Epidermal Growth Factor Enhances Healing of Diabetic Foot Ulcers

Human Epidermal Growth Factor Enhances Healing of Diabetic Foot Ulcers

Chronic Venous Insufficiency and Venous Ulceration

Local application of basic fibroblast growth factor increases the risk of local infection after trauma: An in-vitro and in-vivo study in rats

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