Top

Lasers in Medical Science

Published in:

01-03-2022 | Diabetic Foot | Original Article

Treatment of diabetic foot ulcers in a frail population with severe co-morbidities using at-home photobiomodulation laser therapy: a double-blind, randomized, sham-controlled pilot clinical study

Authors: Amir Haze, Lilach Gavish, Ofer Elishoov, Dorit Shorka, Tamir Tsohar, Yechiel N. Gellman, Meir Liebergall

Published in: Lasers in Medical Science | Issue 2/2022

Abstract

Purpose

To evaluate the safety and efficacy of an at-home photobiomodulation (PBM) device for the treatment of diabetic foot ulcers (DFUs) in a frail population with severe comorbidities.

Methods

Prospective, randomized, double-blind, sham-controlled pilot study. Patients (age = 63 ± 11 years, male:female 13:7) with insulin-dependent diabetes type 2, neuropathy, peripheral artery disease, significant co-morbidities, and large osteomyelitis-associated DFUs (University of Texas grade ≥ III) were randomized to receive active (n = 10) or sham (n = 10) at-home daily PBM treatments (pulsed near-infrared 808 nm Ga-Al-As laser, 250 mW, 8.8 J/cm²) for up to 12 weeks in addition to standard care. The primary outcome was the %wound size reduction. The secondary was adverse events.

Results

With the numbers available, PBM-treated group had significantly greater %reduction compared to sham (area [cm²], baseline vs endpoint: PBM 10[20.3] cm² vs 0.2[2.4] cm²; sham, 7.9 [12.0] cm² vs 4.6 [13.8] cm², p = 0.018 by Mann–Whitney U test). Wound closure > 90% occurred in 7 of 10 PBM-treated patients but in only 1 of 10 sham patients (p = 0.006). No adverse device effects were observed.

Conclusions

Photobiomodulation at home, in addition to standard care, may be effective for the treatment of severe DFUs in frail patients with co-morbidities and is particularly relevant at these times of social distancing. Our preliminary results justify the conduction of a larger clinical trial. ClinicalTrials.gov: NCT01493895.

Available only for authorised users

Armstrong DG, Boulton AJM, Bus SA (2017) Diabetic foot ulcers and their recurrence. N Engl J Med 376(24):2367–2375. https://doi.org/10.1056/NEJMra1615439CrossRefPubMed

Thorud JC, Plemmons B, Buckley CJ, Shibuya N, Jupiter DC (2016) Mortality after nontraumatic major amputation among patients with diabetes and peripheral vascular disease: a systematic review. J Foot Ankle Surg 55(3):591–599. https://doi.org/10.1053/j.jfas.2016.01.012CrossRefPubMed

Jeffcoate WJ, Vileikyte L, Boyko EJ, Armstrong DG, Boulton AJM (2018) Current challenges and opportunities in the prevention and management of diabetic foot ulcers. Diabetes Care 41(4):645–652. https://doi.org/10.2337/dc17-1836CrossRefPubMed

Everett E, Mathioudakis N (2018) Update on management of diabetic foot ulcers. Ann N Y Acad Sci 1411(1):153–165. https://doi.org/10.1111/nyas.13569CrossRefPubMedPubMedCentral

Tchanque-Fossuo CN, Ho D, Dahle SE, Koo E, Isseroff RR, Jagdeo J (2016) Low-level light therapy for treatment of diabetic foot ulcer: a review of clinical experiences. J Drugs Dermatol 15(7):843–848PubMed

Chung H, Dai T, Sharma SK, Huang YY, Carroll JD, Hamblin MR (2012) The nuts and bolts of low-level laser (light) therapy. Ann Biomed Eng 40(2):516–533. https://doi.org/10.1007/s10439-011-0454-7CrossRefPubMed

Anders JJ, Lanzafame RJ, Arany PR (2015) Low-level light/laser therapy versus photobiomodulation therapy. Photomed Laser Surg 33(4):183–184. https://doi.org/10.1089/pho.2015.9848CrossRefPubMedPubMedCentral

Gavish L (2013) Chapter 50: Low-Level laser therapy for wound healing. In: Hamblin M, Huang Y (eds) Handbook of Photomedicine. Boca Raton: CRC Press.,

Houreld NN (2014) Shedding light on a new treatment for diabetic wound healing: a review on phototherapy. ScientificWorldJournal 2014:398412. https://doi.org/10.1155/2014/398412CrossRefPubMedPubMedCentral

10.

Carvalho AF, Feitosa MC, Coelho NP, Rebelo VC, Castro JG, Sousa PR, Feitosa VC, Arisawa EA (2016) Low-level laser therapy and Calendula officinalis in repairing diabetic foot ulcers. Rev Esc Enferm USP 50(4):628–634. https://doi.org/10.1590/S0080-623420160000500013CrossRefPubMed

11.

El-Kader S, M., Ashmawy E, M. (2015) Impact of different therapeutic modalities on healing of diabetic foot ulcers. Eur J Gen Med 12(4):319–325

12.

Feitosa MC, Carvalho AF, Feitosa VC, Coelho IM, Oliveira RA, Arisawa EA (2015) Effects of the low-level laser therapy (LLLT) in the process of healing diabetic foot ulcers. Acta Cir Bras 30(12):852–857. https://doi.org/10.1590/S0102-865020150120000010CrossRefPubMed

13.

Mathur RK, Sahu K, Saraf S, Patheja P, Khan F, Gupta PK (2017) Low-level laser therapy as an adjunct to conventional therapy in the treatment of diabetic foot ulcers. Lasers Med Sci 32(2):275–282. https://doi.org/10.1007/s10103-016-2109-2CrossRefPubMed

14.

Ortíz MCS, Villabona EH, Lemos DMC, Castellanos R (2014) Effects of low level laser therapy and high voltage stimulation on diabetic wound healing. Rev Univ Ind Santander Salud [online] 46(2):107–117

15.

Frangez I, Nizic-Kos T, Frangez HB (2018) Phototherapy with LED shows promising results in healing chronic wounds in diabetes mellitus patients: a prospective randomized double-blind study. Photomed Laser Surg 36(7):377–382. https://doi.org/10.1089/pho.2017.4382CrossRefPubMed

16.

Priyadarshini LMJ, Babu KEP, Thariq IA (2018) Effect of low level laser therapy on diabetic foot ulcers: a randomized control trial. Int Surg J 5(3):1008–1015CrossRef

17.

Sangma MB, Selvaraju S, Marak F, Dasiah SD (2019) Efficacy of low level infrared light therapy on wound healing in patients with chronic diabetic foot ulcers: a randomised control trial. Int Surg J 6(5):1650–1653CrossRef

18.

Flanagan M (2003) Wound measurement can it help us to monitor progression to healing? J Wound Care 12(5):189–194. https://doi.org/10.12968/jowc.2003.12.5.26493CrossRefPubMed

19.

Kajagar BM, Godhi AS, Pandit A, Khatri S (2012) Efficacy of low level laser therapy on wound healing in patients with chronic diabetic foot ulcers-a randomised control trial. Indian J Surg 74(5):359–363. https://doi.org/10.1007/s12262-011-0393-4CrossRefPubMedPubMedCentral

20.

Kaviani A, Djavid GE, Ataie-Fashtami L, Fateh M, Ghodsi M, Salami M, Zand N, Kashef N, Larijani B (2011) A randomized clinical trial on the effect of low-level laser therapy on chronic diabetic foot wound healing: a preliminary report. Photomed Laser Surg 29(2):109–114. https://doi.org/10.1089/pho.2009.2680CrossRefPubMed

21.

Landau Z, Migdal M, Lipovsky A, Lubart R (2011) Visible light-induced healing of diabetic or venous foot ulcers: a placebo-controlled double-blind study. Photomed Laser Surg 29(6):399–404. https://doi.org/10.1089/pho.2010.2858CrossRefPubMed

22.

Minatel DG, Frade MA, Franca SC, Enwemeka CS (2009) Phototherapy promotes healing of chronic diabetic leg ulcers that failed to respond to other therapies. Lasers Surg Med 41(6):433–441. https://doi.org/10.1002/lsm.20789CrossRefPubMed

23.

Maiya AG, Kumar AS, Hazari A, Jadhav R, Ramachandra L, Hande HM, Rajgopal SK, Maiya SG, Kalkura P, Keni LG (2018) Photobiomodulation therapy in neuroischaemic diabetic foot ulcers a novel method of limb salvage. J Wound Care 27(12):837–842. https://doi.org/10.12968/jowc.2018.27.12.837CrossRefPubMed

24.

Del Vecchio A, Floravanti M, Boccassini A, Gaimari G, Vestri A, Di Paolo C, Romeo U (2019) Evaluation of the efficacy of a new low-level laser therapy home protocol in the treatment of temporomandibular joint disorder-related pain: a randomized, double-blind, placebo-controlled clinical trial. Cranio:1–10. https://doi.org/10.1080/08869634.2019.1599174

25.

Fornaini C, Pelosi A, Queirolo V, Vescovi P, Merigo E (2015) The “at-home LLLT” in temporo-mandibular disorders pain control: a pilot study. Laser therapy 24(1):47–52. https://doi.org/10.5978/islsm.15-OR-06CrossRefPubMedPubMedCentral

26.

Merigo E, Rocca JP, Oppici A, Cella L, Fornaini C (2017) At-home laser treatment of oral neuronal disorders: Case reports. J Clin Exp Dent 9(4):e595–e598. https://doi.org/10.4317/jced.53373CrossRefPubMedPubMedCentral

27.

Gavish L, Houreld NN (2019) Therapeutic efficacy of home-use photobiomodulation devices: a systematic literature review. Photobiomodul Photomed Laser Surg 37(1):4–16. https://doi.org/10.1089/photob.2018.4512CrossRefPubMed

28.

Raizman R, Gavish L (2020) At-home self-applied photobiomodulation device for the treatment of diabetic foot ulcers in adults with type 2 diabetes: report of 4 cases. Can J Diabetes 44(5):375–378. https://doi.org/10.1016/j.jcjd.2020.01.010CrossRefPubMed

29.

Merigo E, Tan L, Zhao Z, Rocca J-P, Fornaini C (2020) Auto-administered photobiomodulation on diabetic leg ulcers treatment: a new way to manage it? Case Rep Med 2020:7428472. https://doi.org/10.1155/2020/7428472

30.

Davis FM, Kimball A, Boniakowski A, Gallagher K (2018) Dysfunctional wound healing in diabetic foot ulcers: new crossroads. Curr Diab Rep 18(1):2. https://doi.org/10.1007/s11892-018-0970-zCrossRefPubMed

31.

Buys AV, Van Rooy MJ, Soma P, Van Papendorp D, Lipinski B, Pretorius E (2013) Changes in red blood cell membrane structure in type 2 diabetes: a scanning electron and atomic force microscopy study. Cardiovasc Diabetol 12:25. https://doi.org/10.1186/1475-2840-12-25CrossRefPubMedPubMedCentral

32.

Ziegler O, Guerci B, Muller S, Candiloros H, Mejean L, Donner M, Stoltz JF, Drouin P (1994) Increased erythrocyte aggregation in insulin-dependent diabetes mellitus and its relationship to plasma factors: a multivariate analysis. Metabolism 43(9):1182–1186. https://doi.org/10.1016/0026-0495(94)90063-9CrossRefPubMed

33.

Singh M, Shin S (2009) Changes in erythrocyte aggregation and deformability in diabetes mellitus: a brief review. Indian J Exp Biol 47(1):7–15PubMed

34.

Schindl A, Merwald H, Schindl L, Kaun C, Wojta J (2003) Direct stimulatory effect of low-intensity 670 nm laser irradiation on human endothelial cell proliferation. Br J Dermatol 148(2):334–336CrossRef

35.

Chen CH, Hung HS, Hsu SH (2008) Low-energy laser irradiation increases endothelial cell proliferation, migration, and eNOS gene expression possibly via PI3K signal pathway. Lasers Surg Med 40(1):46–54CrossRef

36.

Kipshidze N, Nikolaychik V, Keelan MH, Shankar LR, Khanna A, Kornowski R, Leon M, Moses J (2001) Low-power helium: neon laser irradiation enhances production of vascular endothelial growth factor and promotes growth of endothelial cells in vitro. Lasers Surg Med 28(4):355–364CrossRef

37.

Gavish L, Perez L, Gertz SD (2006) Low-level laser irradiation modulates matrix metalloproteinase activity and gene expression in porcine aortic smooth muscle cells. Lasers Surg Med 38(8):779–786. https://doi.org/10.1002/lsm.20383CrossRefPubMed

38.

Hawkins D, Abrahamse H (2006) Effect of multiple exposures of low-level laser therapy on the cellular responses of wounded human skin fibroblasts. Photomed Laser Surg 24(6):705–714. https://doi.org/10.1089/pho.2006.24.705CrossRefPubMed

39.

Houreld N, Abrahamse H (2007) Irradiation with a 632.8 nm helium-neon laser with 5 J/cm2 stimulates proliferation and expression of interleukin-6 in diabetic wounded fibroblast cells. Diabetes Technol Ther 9(5):451–459CrossRef

40.

Tuby H, Maltz L, Oron U (2006) Modulations of VEGF and iNOS in the rat heart by low level laser therapy are associated with cardioprotection and enhanced angiogenesis. Lasers Surg Med 38(7):682–688. https://doi.org/10.1002/lsm.20377CrossRefPubMed

41.

Gavish L, Perez LS, Reissman P, Gertz SD (2008) Irradiation with 780 nm diode laser attenuates inflammatory cytokines but upregulates nitric oxide in lipopolysaccharide-stimulated macrophages: implications for the prevention of aneurysm progression. Lasers Surg Med 40(5):371–378. https://doi.org/10.1002/lsm.20635CrossRefPubMed

42.

Bagheri M, Amini A, Abdollahifar MA, Ghoreishi SK, Piryaei A, Pouriran R, Chien S, Dadras S, Rezaei F, Bayat M (2018) Effects of photobiomodulation on degranulation and number of mast cells and wound strength in skin wound healing of streptozotocin-induced diabetic rats. Photomed Laser Surg 36(8):415–423. https://doi.org/10.1089/pho.2018.4453CrossRefPubMed

43.

Kilik R, Lakyova L, Sabo J, Kruzliak P, Lacjakova K, Vasilenko T, Vidova M, Longauer F, Radonak J (2014) Effect of equal daily doses achieved by different power densities of low-level laser therapy at 635 nm on open skin wound healing in normal and diabetic rats. Biomed Res Int 2014:269253. https://doi.org/10.1155/2014/269253CrossRefPubMedPubMedCentral

44.

Mi XQ, Chen JY, Liang ZJ, Zhou LW (2004) In vitro effects of helium-neon laser irradiation on human blood: blood viscosity and deformability of erythrocytes. Photomed Laser Surg 22(6):477–482. https://doi.org/10.1089/pho.2004.22.477CrossRefPubMed

45.

Keszler A, Lindemer B, Weihrauch D, Jones D, Hogg N, Lohr NL (2017) Red/near infrared light stimulates release of an endothelium dependent vasodilator and rescues vascular dysfunction in a diabetes model. Free Radic Biol Med 113:157–164. https://doi.org/10.1016/j.freeradbiomed.2017.09.012CrossRefPubMedPubMedCentral

46.

Santos NR, dos Santos JN, dos Reis JA, Jr., Oliveira PC, de Sousa AP, de Carvalho CM, Soares LG, Marques AM, Pinheiro AL, (2010) Influence of the use of laser phototherapy (lambda660 or 790 nm) on the survival of cutaneous flaps on diabetic rats. Photomed Laser Surg 28(4):483–488. https://doi.org/10.1089/pho.2009.2500CrossRefPubMed

47.

Gavish L, Hoffer O, Rabin N, Halak M, Shkilevich S, Shayovitz Y, Weizman G, Haim O, Gavish B, Gertz SD, Ovadia-Blechman Z (2020) Microcirculatory response to photobiomodulation – why some respond and others do not: a randomised controlled study. Lasers Surg Med 52(9):863–872CrossRef

48.

Samoilova KA, Zhevago NA, Petrishchev NN, Zimin AA (2008) Role of nitric oxide in the visible light induced rapid increase of human skin microcirculation at the local and systemic levels II healthy volunteers. Photomed Laser Surg 26(5):443–449. https://doi.org/10.1089/pho.2007.2205CrossRefPubMed

49.

Samoilova KA, Zhevago NA, Menshutina MA, Grigorieva NB (2008) Role of nitric oxide in the visible light induced rapid increase of human skin microcirculation at the local and systemic level I diabetic patients. Photomed Laser Surg 26(5):433–442. https://doi.org/10.1089/pho.2007.2197CrossRefPubMed

50.

Schindl A, Schindl M, Schon H, Knobler R, Havelec L, Schindl L (1998) Low-intensity laser irradiation improves skin circulation in patients with diabetic microangiopathy. Diabetes Care 21(4):580–584CrossRef

51.

Administration FaD (June 2006) Guidance for industry chronic cutaneous ulcer and burn wounds — developing products for treatment. Rockville, MD

Title: Treatment of diabetic foot ulcers in a frail population with severe co-morbidities using at-home photobiomodulation laser therapy: a double-blind, randomized, sham-controlled pilot clinical study
Authors: Amir Haze
Lilach Gavish
Ofer Elishoov
Dorit Shorka
Tamir Tsohar
Yechiel N. Gellman
Meir Liebergall
Publication date: 01-03-2022
Publisher: Springer London
Keywords: Diabetic Foot
Laser
Published in: Lasers in Medical Science / Issue 2/2022
Print ISSN: 0268-8921
Electronic ISSN: 1435-604X
DOI: https://doi.org/10.1007/s10103-021-03335-9

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Treatment of diabetic foot ulcers in a frail population with severe co-morbidities using at-home photobiomodulation laser therapy: a double-blind, randomized, sham-controlled pilot clinical study

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2022

Detection of hypokalemia disorder and its relation with hypercalcemia in blood serum using LIBS technique for patients of colorectal cancer grade I and grade II

Efficacy of 5-aminolevulinic acid-based photodynamic therapy in different subtypes of canine mammary gland cancer cells

Clinical effectiveness of adjunctive diode laser on scaling and root planing in the treatment of periodontitis: is there an optimal combination of usage mode and application regimen? A systematic review and meta-analysis

What else than eyes need special protectors during laser hair reduction sessions?

Effect of antimicrobial photodynamic therapy with red led and methylene blue on the reduction of halitosis: controlled microbiological clinical trial

Efficacy of near infrared dental lasers on dentinal hypersensitivity: a meta-analysis of randomized controlled clinical trials