Treatment of Symptomatic Bilateral Knee Osteoarthritis: Intra-articular Injection of Autologous Microfragmented Adipose Tissue and Hyaluronic Acid vs Intra Articular Injection of Autologous Microfragmented Adipose Tissue

Summary

The HYALOFAT study is a randomized controlled double-blind trial with parallel treatment arms and 1:1 allocation. By means of a double-blind randomized controlled trial in patients with symptomatic bilateral OA of the knees, the clinical outcomes of autologous microfragmented adipose tissue injection associated with hyaluronic acid in one knee vs autologous microfragmented adipose tissue injection in the contralateral knee will be evaluated and compared. Each patient will then serve as his or her own control and not be informed of the knee assigned to the treatment group. In addition, it will be the aim of the study to evaluate the safety of the combined treatment by documenting any adverse events.

Timeline

Start

2025-09-29

Primary completion

2030-09

Completion

2030-09

Publications

• Background Holzbauer M, Priglinger E, Kolle ST, Prantl L, Stadler C, Winkler PW, Gotterbarm T, Duscher D. Intra-Articular Application of Autologous, Fat-Derived Orthobiologics in the Treatment of Knee Osteoarthritis: A Systematic Review. Cells. 2024 Apr 25;13(9):750. doi: 10.3390/cells13090750.
• Background Bianchi F, Maioli M, Leonardi E, Olivi E, Pasquinelli G, Valente S, Mendez AJ, Ricordi C, Raffaini M, Tremolada C, Ventura C. A new nonenzymatic method and device to obtain a fat tissue derivative highly enriched in pericyte-like elements by mild mechanical forces from human lipoaspirates. Cell Transplant. 2013;22(11):2063-77. doi: 10.3727/096368912X657855. Epub 2012 Oct 8.
• Background Tremolada C, Palmieri G, Ricordi C. Adipocyte transplantation and stem cells: plastic surgery meets regenerative medicine. Cell Transplant. 2010;19(10):1217-23. doi: 10.3727/096368910X507187. Epub 2010 May 4.
• Background Perdisa F, Gostynska N, Roffi A, Filardo G, Marcacci M, Kon E. Adipose-Derived Mesenchymal Stem Cells for the Treatment of Articular Cartilage: A Systematic Review on Preclinical and Clinical Evidence. Stem Cells Int. 2015;2015:597652. doi: 10.1155/2015/597652. Epub 2015 Jul 9.
• Background Van Pham P, Hong-Thien Bui K, Quoc Ngo D, Tan Khuat L, Kim Phan N. Transplantation of Nonexpanded Adipose Stromal Vascular Fraction and Platelet-Rich Plasma for Articular Cartilage Injury Treatment in Mice Model. J Med Eng. 2013;2013:832396. doi: 10.1155/2013/832396. Epub 2013 Jan 16.
• Background Jurgens WJ, Kroeze RJ, Zandieh-Doulabi B, van Dijk A, Renders GA, Smit TH, van Milligen FJ, Ritt MJ, Helder MN. One-step surgical procedure for the treatment of osteochondral defects with adipose-derived stem cells in a caprine knee defect: a pilot study. Biores Open Access. 2013 Aug;2(4):315-25. doi: 10.1089/biores.2013.0024.
• Background Filardo G, Tschon M, Perdisa F, Brogini S, Cavallo C, Desando G, Giavaresi G, Grigolo B, Martini L, Nicoli Aldini N, Roffi A, Fini M, Kon E. Micro-fragmentation is a valid alternative to cell expansion and enzymatic digestion of adipose tissue for the treatment of knee osteoarthritis: a comparative preclinical study. Knee Surg Sports Traumatol Arthrosc. 2022 Mar;30(3):773-781. doi: 10.1007/s00167-020-06373-y. Epub 2021 Jan 19.
• Background Perucca Orfei C, Boffa A, Sourugeon Y, Laver L, Magalon J, Sanchez M, Tischer T, Filardo G, de Girolamo L. Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 1: adipose tissue-derived cell-based injectable therapies. Knee Surg Sports Traumatol Arthrosc. 2023 Feb;31(2):641-655. doi: 10.1007/s00167-022-07063-7. Epub 2022 Sep 14.
• Background Vezzani B, Shaw I, Lesme H, Yong L, Khan N, Tremolada C, Peault B. Higher Pericyte Content and Secretory Activity of Microfragmented Human Adipose Tissue Compared to Enzymatically Derived Stromal Vascular Fraction. Stem Cells Transl Med. 2018 Dec;7(12):876-886. doi: 10.1002/sctm.18-0051. Epub 2018 Sep 26.
• Background Desando G, Bartolotti I, Martini L, Giavaresi G, Nicoli Aldini N, Fini M, Roffi A, Perdisa F, Filardo G, Kon E, Grigolo B. Regenerative Features of Adipose Tissue for Osteoarthritis Treatment in a Rabbit Model: Enzymatic Digestion Versus Mechanical Disruption. Int J Mol Sci. 2019 May 29;20(11):2636. doi: 10.3390/ijms20112636.
• Background Pak J. Regeneration of human bones in hip osteonecrosis and human cartilage in knee osteoarthritis with autologous adipose-tissue-derived stem cells: a case series. J Med Case Rep. 2011 Jul 7;5:296. doi: 10.1186/1752-1947-5-296.
• Background Zaffagnini S, Andriolo L, Boffa A, Poggi A, Cenacchi A, Busacca M, Kon E, Filardo G, Di Martino A. Microfragmented Adipose Tissue Versus Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: A Prospective Randomized Controlled Trial at 2-Year Follow-up. Am J Sports Med. 2022 Sep;50(11):2881-2892. doi: 10.1177/03635465221115821. Epub 2022 Aug 19.
• Background Veronesi F, Andriolo L, Salerno M, Boffa A, Giavaresi G, Filardo G. Adipose Tissue-Derived Minimally Manipulated Products versus Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: A Systematic Review of Clinical Evidence and Meta-Analysis. J Clin Med. 2023 Dec 22;13(1):67. doi: 10.3390/jcm13010067.
• Background Qiao X, Yan L, Feng Y, Li X, Zhang K, Lv Z, Xu C, Zhao S, Liu F, Yang X, Tian Z. Efficacy and safety of corticosteroids, hyaluronic acid, and PRP and combination therapy for knee osteoarthritis: a systematic review and network meta-analysis. BMC Musculoskelet Disord. 2023 Nov 30;24(1):926. doi: 10.1186/s12891-023-06925-6.
• Background Howlader MAA, Almigdad A, Urmi JF, Ibrahim H. Efficacy and Safety of Hyaluronic Acid and Platelet-Rich Plasma Combination Therapy Versus Platelet-Rich Plasma Alone in Treating Knee Osteoarthritis: A Systematic Review. Cureus. 2023 Oct 18;15(10):e47256. doi: 10.7759/cureus.47256. eCollection 2023 Oct.
• Background Corradetti B, Taraballi F, Martinez JO, Minardi S, Basu N, Bauza G, Evangelopoulos M, Powell S, Corbo C, Tasciotti E. Hyaluronic acid coatings as a simple and efficient approach to improve MSC homing toward the site of inflammation. Sci Rep. 2017 Aug 11;7(1):7991. doi: 10.1038/s41598-017-08687-3.
• Background Li L, Duan X, Fan Z, Chen L, Xing F, Xu Z, Chen Q, Xiang Z. Mesenchymal Stem Cells in Combination with Hyaluronic Acid for Articular Cartilage Defects. Sci Rep. 2018 Jul 2;8(1):9900. doi: 10.1038/s41598-018-27737-y.
• Background Auw Yang KG, Raijmakers NJ, van Arkel ER, Caron JJ, Rijk PC, Willems WJ, Zijl JA, Verbout AJ, Dhert WJ, Saris DB. Autologous interleukin-1 receptor antagonist improves function and symptoms in osteoarthritis when compared to placebo in a prospective randomized controlled trial. Osteoarthritis Cartilage. 2008 Apr;16(4):498-505. doi: 10.1016/j.joca.2007.07.008. Epub 2007 Sep 6.
• Background Bellamy N, Hochberg M, Tubach F, Martin-Mola E, Awada H, Bombardier C, Hajjaj-Hassouni N, Logeart I, Matucci-Cerinic M, van de Laar M, van der Heijde D, Dougados M. Development of multinational definitions of minimal clinically important improvement and patient acceptable symptomatic state in osteoarthritis. Arthritis Care Res (Hoboken). 2015 Jul;67(7):972-80. doi: 10.1002/acr.22538.

Drugs

Indications