Macrophage stimulating agent soluble yeast β-1,3/1,6-glucan as a topical treatment of diabetic foot and leg ulcers: A randomized, double blind, placebo-controlled phase II study

Svetlana N Zykova, Ksenia A Balandina, Natalia V Vorokhobina, Alla V Kuznetsova, Rolf Engstad, Tatiana A Zykova, Svetlana N Zykova, Ksenia A Balandina, Natalia V Vorokhobina, Alla V Kuznetsova, Rolf Engstad, Tatiana A Zykova

Abstract

Aims/introduction: Dysregulated inflammatory response is believed to be an important factor in the pathogenesis of several late complications of diabetes mellitus. β-Glucans are potent inducers of immune function. The present randomized, double blind, two-center, placebo-controlled study was undertaken to explore safety, tolerability and efficacy of soluble β-1,3/1,6-glucan (SBG) as a local treatment of diabetic foot ulcers.

Materials and methods: A total of 60 patients with type 1 or 2 diabetes and lower extremity ulcers (Wagner grade 1-2, Ankle/Brachial Index ≥0.7) received SBG or a comparator product (methylcellulose) locally three times weekly up to 12 weeks in addition to conventional management scheme. A total of 54 patients completed the study.

Results: A tendency for shorter median time to complete healing in the SBG group was observed (36 vs 63 days, P = 0.130). Weekly percentage reduction in ulcer size was significantly higher in the SBG group than in the methylcellulose group between weeks 1-2, 3-4 and 5-6 (P < 0.05). The proportion of ulcers healed by week 12 was also in favor of SBG (59% vs 37%, P = 0.09), with a significantly higher healing incidence in the SBG group at week 8 (44% vs 17%, P = 0.03). SBG was safe and well tolerated. There was a clinically significant difference regarding the incidence of serious adverse events in favor of the SBG treatment.

Conclusions: Local treatment of diabetic lower extremity ulcers with β-1,3/1,6-polyglucose shows good safety results. This β-glucan preparation shows promising potential as a treatment accelerating cutaneous healing. Further studies are required to confirm this effect. This trial was registered with ClinicalTrials.gov (no. NCT00288392).

Keywords: Diabetic foot; Wound healing; β‐Glucans.

Figures

Figure 1
Figure 1
Disposition of patients.
Figure 2
Figure 2
Cumulative rate of complete ulcer healing in response to local treatment with soluble β‐1,3/1,6‐glucan (SBG) or methylcellulose (placebo). Differences between the curves were tested by a log–rank test (P = 0.0944).
Figure 3
Figure 3
Accumulated median percentage wound size reduction during the 12‐week treatment period (per protocol ulcer). SBG, soluble β‐1,3/1,6‐glucan.
Figure 4
Figure 4
Percentage of completely healed wounds at week 8 of treatment in the different patient populations. Equality of response between the two treatment arms was tested with chi‐squared‐test. P‐values as shown in the figure. ITT‐Patient, intention‐to‐treat patient population; ITT‐Ulcer, intention‐to‐treat ulcer population; PP‐Patient, per protocol patient population; PP‐Ulcer, per protocol ulcer population.

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