Top

Published in:

01-12-2020 | Knee Osteoarthritis | Study protocol

Autologous adipose tissue injection versus platelet-rich plasma (PRP) injection in the treatment of knee osteoarthritis: a randomized, controlled study – study protocol

Authors: Paweł Bąkowski, Jakub Kaszyński, Joanna Wałecka, Kinga Ciemniewska-Gorzela, Kamilla Bąkowska-Żywicka, Tomasz Piontek

Published in: BMC Musculoskeletal Disorders | Issue 1/2020

Abstract

Background

Knee osteoarthritis (OA) is a common, chronic, progressive and degenerative disease which affects patients’ quality of life and may cause disability and social isolation. OA is a huge economic burden for the patient and a large strain for the whole healthcare system. Articular cartilage has a small potential to repair, with progressively more clinicians emphasizing cellular therapy. Subcutaneous fat tissue in human body is a large reservoir of mesenchymal stem cells (MSCs) and is been harvested in minimally invasive, simple procedure. Up to date there is no prospective randomized controlled studies demonstrating effectiveness and role of adipose tissue injections in OA treatment. The purpose of this study is to assess functional and clinical changes among patients with symptomatic knee OA treated with intra-articular injections of autologous adipose tissue or platelet rich plasma (PRP) and to compare efficacy of both therapeutic methods.

Methods

This is a prospective, randomized, controlled study. Patients who meet inclusion criteria will be allocated to Fat Tissue group or PRP group randomly. Subjects will receive an intra articular injection with autologous adipose tissue and PRP respectively. Patients will be assessed five times: before treatment and 1, 3, 6 and 12 months after the treatment. The assessment consists of patient reported outcome measures (The Knee injury and Osteoarthritis Outcome Score, International Knee Documentation Committee 2000, the Western Ontario and McMaster Universities Osteoarthritis Index, the Health Questionnaire EQ- 5D- 5 L), three functional tests (The Timed Up and Go Test, The 5 Times Sit to Stand Test, The 10 m Walk Test) and Maximal Isometric Voluntary Contraction.

Discussion

This study protocol has several strengths and weaknesses. One of strongest point of this study is the wide, multidimensional functional assessment which will give a large amount of objective data. On the other hand, lack of blinding has to be considered as a risk of both subject and investigator bias.

Trial registration

name of registry: ClinicalTrials.gov, trial registration number: NCT04321629, retrospectively registered on date of registration.

Chahla J, Mandelbaum BR. Biological treatment for osteoarthritis of the knee: moving from bench to bedside-current practical concepts. Arthroscopy. 2018;34(5):1719–29. https://doi.org/10.1016/j.arthro.2018.01.048.CrossRefPubMed

Hermann W, Lambova S, Muller-Ladner U. Current treatment options for osteoarthritis. Curr Rheumatol Rev. 2018;14(2):108–16. https://doi.org/10.2174/1573397113666170829155149.CrossRefPubMed

Samson DJ, Grant MD, Ratko TA, Bonnell CJ, Ziegler KM, Aronson N. Treatment of primary and secondary osteoarthritis of the knee. Evid Rep. Technol Assess (Full Rep). 2007;(157):1–157.

Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bull World Health Organ. 2003;81(9):646–56.PubMedPubMedCentral

Hiligsmann M, Cooper C, Arden N, et al. Health economics in the field of osteoarthritis: an expert's consensus paper from the European Society for Clinical and Economic Aspects of osteoporosis and osteoarthritis (ESCEO). Semin Arthritis Rheum. 2013;43(3):303–13. https://doi.org/10.1016/j.semarthrit.2013.07.003.CrossRefPubMed

Bartholdy C, Juhl C, Christensen R, Lund H, Zhang W, Henriksen M. The role of muscle strengthening in exercise therapy for knee osteoarthritis: a systematic review and meta-regression analysis of randomized trials. Semin Arthritis Rheum. 2017;47(1):9–21. https://doi.org/10.1016/j.semarthrit.2017.03.007.CrossRefPubMed

Bartels EM, Juhl CB, Christensen R, et al. Aquatic exercise for the treatment of knee and hip osteoarthritis. Cochrane Database Syst Rev. 2016;3:CD005523. https://doi.org/10.1002/14651858.CD005523.pub3.CrossRefPubMed

Delanois RE, Etcheson JI, Sodhi N, et al. Biologic therapies for the treatment of knee osteoarthritis. J Arthroplast. 2019;34(4):801–13. https://doi.org/10.1016/j.arth.2018.12.001.CrossRef

Meheux CJ, McCulloch PC, Lintner DM, Varner KE, Harris JD. Efficacy of intra-articular platelet-rich plasma injections in knee osteoarthritis: a systematic review. Arthroscopy. 2016;32(3):495–505. https://doi.org/10.1016/j.arthro.2015.08.005.CrossRefPubMed

10.

Dai WL, Zhou AG, Zhang H, Zhang J. Efficacy of platelet-rich plasma in the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials. Arthroscopy. 2017;33(3):659–670.e1. https://doi.org/10.1016/j.arthro.2016.09.024.CrossRefPubMed

11.

Xing D, Wang B, Zhang W, et al. Intra-articular platelet-rich plasma injections for knee osteoarthritis: An overview of systematic reviews and risk of bias considerations. Int J Rheum Dis. 2017;20(11):1612–30. https://doi.org/10.1111/1756-185X.13233.CrossRefPubMed

12.

Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. 2013;41(2):356–64. https://doi.org/10.1177/0363546512471299.CrossRefPubMed

13.

Garay-Mendoza D, Villarreal-Martínez L, Garza-Bedolla A, et al. The effect of intra-articular injection of autologous bone marrow stem cells on pain and knee function in patients with osteoarthritis. Int J Rheum Dis. 2018;21(1):140–7. https://doi.org/10.1111/1756-185X.13139.CrossRefPubMed

14.

Bianchi F, Maioli M, Leonardi E, et al. 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. https://doi.org/10.3727/096368912X657855.CrossRefPubMed

15.

Schiavone Panni A, Vasso M, Braile A, et al. Preliminary results of autologous adipose-derived stem cells in early knee osteoarthritis: identification of a subpopulation with greater response. Int Orthop. 2019;43(1):7–13. https://doi.org/10.1007/s00264-018-4182-6.CrossRefPubMed

16.

Roos EM, Lohmander LS. The knee injury and osteoarthritis outcome score (KOOS): from joint injury to osteoarthritis. Health Qual Life Outcomes. 2003;1:64. https://doi.org/10.1186/1477-7525-1-64.CrossRefPubMedPubMedCentral

17.

Paradowski PT, Kęska R, Witoński D. Validation of the polish version of the knee injury and osteoarthritis outcome score (KOOS) in patients with osteoarthritis undergoing total knee replacement. BMJ Open. 2015;5(7):e006947. https://doi.org/10.1136/bmjopen-2014-006947.CrossRefPubMedPubMedCentral

18.

Paradowski PT, Witoński D, Kęska R, Roos EM. Cross-cultural translation and measurement properties of the polish version of the knee injury and osteoarthritis outcome score (KOOS) following anterior cruciate ligament reconstruction. Health Qual Life Outcomes. 2013;11:107. https://doi.org/10.1186/1477-7525-11-107.CrossRefPubMedPubMedCentral

19.

Anderson AF, Irrgang JJ, Kocher MS, Mann BJ, Harrast JJ. International knee documentation committee. The international knee documentation committee subjective knee evaluation form: normative data. Am J Sports Med. 2006;34(1):128–35. https://doi.org/10.1177/0363546505280214.CrossRefPubMed

20.

Piontek T, Ciemniewska-Gorzela K, Naczk J, Cichy K, Szulc A. Linguistic and cultural adaptation into polish of the IKDC 2000 subjective knee evaluation form and the Lysholm scale. Pol Orthop Traumatol. 2012;77:115–9.PubMed

21.

Theiler R, Spielberger J, Bischoff HA, Bellamy N, Huber J, Kroesen S. Clinical evaluation of the WOMAC 3.0 OA index in numeric rating scale format using a computerized touch screen version. Osteoarthr Cartil. 2002;10(6):479–81. https://doi.org/10.1053/joca.2002.0807.CrossRef

22.

Bellamy N, Campbell J, Stevens J, Pilch L, Stewart C, Mahmood Z. Validation study of a computerized version of the Western Ontario and McMaster universities VA3.0 osteoarthritis index. J Rheumatol. 1997;24(12):2413–5.PubMed

23.

Golicki D, Niewada M. EQ-5D-5L polish population norms. Arch Med Sci 2017;13(1):191–200. doi:https://doi.org/10.5114/aoms.2015.52126.CrossRef

24.

Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20(10):1727–36. https://doi.org/10.1007/s11136-011-9903-x.CrossRefPubMedPubMedCentral

25.

Yeung TS, Wessel J, Stratford PW, MacDermid JC. The timed up and go test for use on an inpatient orthopaedic rehabilitation ward. J Orthop Sports Phys Ther. 2008;38(7):410–7. https://doi.org/10.2519/jospt.2008.2657.CrossRefPubMed

26.

Goldberg A, Chavis M, Watkins J, Wilson T. The five-times-sit-to-stand test: validity, reliability and detectable change in older females. Aging Clin Exp Res. 2012;24(4):339–44. https://doi.org/10.1007/BF03325265.CrossRefPubMed

27.

Fearon A, Neeman T, Smith P, Scarvell J, Cook J. Pain, not structural impairments may explain activity limitations in people with gluteal tendinopathy or hip osteoarthritis: a cross sectional study. Gait Posture. 2017;52:237–43. https://doi.org/10.1016/j.gaitpost.2016.12.005.CrossRefPubMed

28.

Roos EM, Lohmander LS. The Knee injury and Osteoarthritis Outcome Score (KOOS): from joint injury to osteoarthritis. Health Qual Life Outcomes. 2003;1:64. Published 2003 Nov 3. https://doi.org/10.1186/1477-7525-1-64.CrossRefPubMedPubMedCentral

29.

KOOS User’s Guide. 2003. http://www.koos.nu/KOOSGuide2003.pdf. Accessed 18 May 2020.

30.

Zhu Y, Yuan M, Meng HY, et al. Basic science and clinical application of platelet-rich plasma for cartilage defects and osteoarthritis: a review. Osteoarthr Cartil. 2013;21(11):1627–37. https://doi.org/10.1016/j.joca.2013.07.017.CrossRef

31.

Bennell KL, Hunter DJ, Paterson KL. Platelet-rich plasma for the Management of hip and Knee Osteoarthritis. Curr Rheumatol Rep. 2017;19(5):24. https://doi.org/10.1007/s11926-017-0652-x.CrossRefPubMed

32.

Akeda K, An HS, Okuma M, et al. Platelet-rich plasma stimulates porcine articular chondrocyte proliferation and matrix biosynthesis. Osteoarthr Cartil. 2006;14(12):1272–80. https://doi.org/10.1016/j.joca.2006.05.008.CrossRef

33.

Pereira RC, Scaranari M, Benelli R, et al. Dual effect of platelet lysate on human articular cartilage: a maintenance of chondrogenic potential and a transient proinflammatory activity followed by an inflammation resolution. Tissue Eng Part A. 2013;19(11–12):1476–88. https://doi.org/10.1089/ten.TEA.2012.0225.CrossRefPubMed

34.

Cole BJ, Karas V, Hussey K, Pilz K, Fortier LA. Hyaluronic acid versus platelet-rich plasma: a prospective, double-blind randomized controlled trial comparing clinical outcomes and effects on intra-articular biology for the treatment of knee osteoarthritis [published correction appears in am J sports med. 2017 Apr;45(5):NP10]. Am J Sports Med. 2017;45(2):339–46. https://doi.org/10.1177/0363546516665809.CrossRefPubMed

35.

Anitua E, Sánchez M, Nurden AT, et al. Platelet-released growth factors enhance the secretion of hyaluronic acid and induce hepatocyte growth factor production by synovial fibroblasts from arthritic patients. Rheumatology (Oxford). 2007;46(12):1769–72. https://doi.org/10.1093/rheumatology/kem234.CrossRef

36.

Di Y, Han C, Zhao L, Ren Y. Is local platelet-rich plasma injection clinically superior to hyaluronic acid for treatment of knee osteoarthritis? A systematic review of randomized controlled trials. Arthritis Res Ther. 2018;20(1):128. https://doi.org/10.1186/s13075-018-1621-0.CrossRefPubMedPubMedCentral

37.

Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell. 2011;9(1):11–5. https://doi.org/10.1016/j.stem.2011.06.008.CrossRefPubMedPubMedCentral

38.

Caplan AI. All MSCs are pericytes? Cell Stem Cell. 2008;3(3):229–30. https://doi.org/10.1016/j.stem.2008.08.008.CrossRefPubMed

39.

Caplan AI, Sorrell JM. The MSC curtain that stops the immune system. Immunol Lett. 2015;168(2):136–9. https://doi.org/10.1016/j.imlet.2015.06.005.CrossRefPubMed

40.

Koh YG, Kwon OR, Kim YS, Choi YJ, Tak DH. Adipose-derived Mesenchymal stem cells with microfracture versus microfracture alone: 2-year follow-up of a prospective randomized trial. Arthroscopy. 2016;32(1):97–109. https://doi.org/10.1016/j.arthro.2015.09.010.CrossRefPubMed

41.

Nguyen PD, Tran TD, Nguyen HT, et al. Comparative clinical observation of arthroscopic microfracture in the presence and absence of a stromal vascular fraction injection for osteoarthritis. Stem Cells Transl Med. 2017;6(1):187–95. https://doi.org/10.5966/sctm.2016-0023.CrossRefPubMed

42.

Pers YM, Rackwitz L, Ferreira R, et al. Adipose Mesenchymal stromal cell-based therapy for severe osteoarthritis of the knee: a phase I dose-escalation trial. Stem Cells Transl Med. 2016;5(7):847–56. https://doi.org/10.5966/sctm.2015-0245.CrossRefPubMedPubMedCentral

43.

Kim YS, Choi YJ, Lee SW, et al. Assessment of clinical and MRI outcomes after mesenchymal stem cell implantation in patients with knee osteoarthritis: a prospective study. Osteoarthr Cartil. 2016;24(2):237–45. https://doi.org/10.1016/j.joca.2015.08.009.CrossRef

44.

Cattaneo G, De Caro A, Napoli F, Chiapale D, Trada P, Camera A. Micro-fragmented adipose tissue injection associated with arthroscopic procedures in patients with symptomatic knee osteoarthritis. BMC Musculoskelet Disord. 2018;19(1):176. https://doi.org/10.1186/s12891-018-2105-8.CrossRefPubMedPubMedCentral

45.

Roos EM, Toksvig-Larsen S. Knee injury and osteoarthritis outcome score (KOOS) - validation and comparison to the WOMAC in total knee replacement. Health Qual Life Outcomes. 2003;1:17. https://doi.org/10.1186/1477-7525-1-17.CrossRefPubMedPubMedCentral

46.

Pintat J, Silvestre A, Magalon G, et al. Intra-articular injection of Mesenchymal stem cells and platelet-rich plasma to treat Patellofemoral osteoarthritis: preliminary results of a long-term pilot study. J Vasc Interv Radiol. 2017;28(12):1708–13. https://doi.org/10.1016/j.jvir.2017.08.004.CrossRefPubMed

47.

Pak J, Chang JJ, Lee JH, Lee SH. Safety reporting on implantation of autologous adipose tissue-derived stem cells with platelet-rich plasma into human articular joints. BMC Musculoskelet Disord. 2013;14:337. https://doi.org/10.1186/1471-2474-14-337.CrossRefPubMedPubMedCentral

48.

Fodor PB, Paulseth SG. Adipose derived stromal cell (ADSC) injections for pain Management of Osteoarthritis in the human knee joint. Aesthet Surg J. 2016;36(2):229–36. https://doi.org/10.1093/asj/sjv135.CrossRefPubMed

49.

Spasovski D, Spasovski V, Baščarević Z, et al. Intra-articular injection of autologous adipose-derived mesenchymal stem cells in the treatment of knee osteoarthritis. J Gene Med. 2018;20(1). https://doi.org/10.1002/jgm.3002 doi:10.1002/jgm.3002.CrossRef

50.

Jo CH, Chai JW, Jeong EC, et al. Intra-articular injection of Mesenchymal stem cells for the treatment of osteoarthritis of the knee: a 2-year follow-up study. Am J Sports Med. 2017;45(12):2774–83. https://doi.org/10.1177/0363546517716641.CrossRefPubMed

51.

Lee WS, Kim HJ, Kim KI, Kim GB, Jin W. Intra-articular injection of autologous adipose tissue-derived Mesenchymal stem cells for the treatment of knee osteoarthritis: a phase IIb, randomized, placebo-controlled clinical trial. Stem Cells Transl Med. 2019;8(6):504–11. https://doi.org/10.1002/sctm.18-0122.CrossRefPubMedPubMedCentral

52.

Brazier JE, Harper R, Munro J, Walters SJ, Snaith ML. Generic and condition-specific outcome measures for people with osteoarthritis of the knee. Rheumatology (Oxford). 1999;38(9):870–7. https://doi.org/10.1093/rheumatology/38.9.870.CrossRef

Title: Autologous adipose tissue injection versus platelet-rich plasma (PRP) injection in the treatment of knee osteoarthritis: a randomized, controlled study – study protocol
Authors: Paweł Bąkowski
Jakub Kaszyński
Joanna Wałecka
Kinga Ciemniewska-Gorzela
Kamilla Bąkowska-Żywicka
Tomasz Piontek
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Knee Osteoarthritis
Osteoarthrosis
Autologous Fat
Osteoarthrosis
Knee Osteoarthritis
Published in: BMC Musculoskeletal Disorders / Issue 1/2020
Electronic ISSN: 1471-2474
DOI: https://doi.org/10.1186/s12891-020-03345-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Autologous adipose tissue injection versus platelet-rich plasma (PRP) injection in the treatment of knee osteoarthritis: a randomized, controlled study – study protocol

Abstract

Background

Methods

Discussion

Trial registration

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2020

Diagnosis, preoperative evaluation, classification and total hip arthroplasty in patients with long-term unreduced hip joint dislocation, secondary osteoarthritis and pseudoarthrosis

Large autologous ilium with periosteum for tibiotalar joint reconstruction in Rüedi-Allgöwer III or AO/OTA type C3 pilon fractures: a pilot study

Protocol for a multicenter prospective cohort study evaluating sport activity and development of femoroacetabular impingement in the adolescent hip

Activation of FoxO1/SIRT1/RANKL/OPG pathway may underlie the therapeutic effects of resveratrol on aging-dependent male osteoporosis

Playing sport injured is associated with osteoarthritis, joint pain and worse health-related quality of life: a cross-sectional study

Effect of preoperative vitamin D deficiency on functional outcomes after high tibial osteotomy: a retrospective case control study