Efficacy and Safety of Low-Frequency, Noncontact Airborne Ultrasound Therapy (Glybetac) For Neuropathic Diabetic Foot Ulcers: A Randomized, Double-Blind, Sham-Control Study

Abstract

The diabetic foot ulcer (DFU) healing rates remain dismally low. Therefore, many adjunctive therapies have been evaluated including ultrasound therapy. The prior studies with noncontact, low-frequency ultrasound were retrospective, single arm, unblinded, or with historical controls. The aim of the present study was to compare the efficacy of noncontact, low-frequency airborne ultrasound (Glybetac) therapy with sham therapy added to standard treatment in patients with neuropathic, clinically infected, or noninfected DFU (wound size >2 cm 2), Wagner grades 2 and 3. Patients received ultrasound or sham therapy for 28 days dosed daily for first 6 days followed by twice a week for next 3 weeks along with standard of care. The primary outcome was percentage of patients with at least >50% decrease in wound area at 4 week of intervention. Fifty-eight patients completed the study protocol. The duration of wound was 15.8 ± 11.2 weeks and 12.1 ± 10.9 weeks and wound area of 11.3 ± 8.2 cm 2 and 14.8 ± 13.8 cm 2 (P = .507) in the ultrasound and sham groups, respectively. A >50% reduction in wound area was observed in 97.1% and 73.1% subjects (P = .042) in ultrasound and sham groups, respectively. Wound contraction was faster in the first 2 weeks with ultrasound therapy, 5.3 cm 2 , compared with 3.0 cm 2 (P = .025) with sham treatment. Overall, wound area reduction of 69.4 ± 23.2% and 59.6 ± 24.9% (P = .126) was observed at 4 weeks in the ultrasound and sham groups, respectively. We conclude that the airborne low-frequency ultrasound therapy improves and hastens the healing of chronic neuropathic DFU when combined with standard wound care.

Ultrasound in the Modern Management of the Diabetic Foot Syndrome: A Multipurpose Versatile Toolkit

“…In particular, Rastogi et al 140 observed in a 4-week follow-up period a reduction of the wound area in 97.1% and a percentage of wound healing of 23.5% in the US group compared with the 73.1% (P = .042) and the 11.5% (P = .033) observed in control group, respectively. The results of Ennis et al 144 study also showed a double percentage of wound healing within 90 days and a shorter mean time to healing in group using US therapy compared with the control group.…”

“…The therapeutic use of US has been evaluated in many studies conducted in wounds of different origin, including DFUs. [137][138][139][140][141][142][143][144][145][146][147] The therapeutic-frequency spectrum ranges from 20 to 120 kHz and is applied to wounds directly 148 or to periwound sites or by subaqueous immersion. 149 The rationale of therapeutic US application is based on 2 main mechanisms of action that are involved in the wound healing process [149][150][151][152] : cavitation and microstreaming.…”

“…Their results are reported in Table 2. 140,144,145 Two of these studies demonstrated a significant reduction in ulcer area and a high percentage of complete wound closure compared with sham treatment.…”

“…The therapeutic use of US has been evaluated in many studies conducted in wounds of different origin, including DFUs. 137-147…”

Effect and Mechanism of the Bruton Tyrosine Kinase (Btk) Inhibitor Ibrutinib on Rat Model of Diabetic Foot Ulcers

“…At least 25% of diabetic patients are likely to develop diabetic foot, and 85% of diabetic foot ulcers can eventually lead to amputation [7,8]. Epidemiological studies have reported that due to ischemia caused by diabetic nephropathy or peripheral vascular disease, diabetic distal limb neuropathy might occur, and then develops into diabetic foot [9].…”