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

NCT07121556 | Recruiting

• 1 other identifier: HYALOFAT
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Osteoarthritis Knees Both

Keywords

Osteoarthritis; Knees; HA; Micro-fragmented autologous adipose tissue; Hyaluronic acid; Intra-articular injection; Randomized double-blind study

Outcome Measures

Primary Outcomes (1)

• Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)

  It's a standardized and widely used questionnaire to assess the condition of patients with osteoarthritis of the knee and includes assessment of pain, stiffness, and physical function of the joints. It can be administered to the patient. It measures 5 items for pain (range 0-20), two for stiffness (range 0-8), and 17 for functional limitation (range 0-68) that mainly relate to activities of daily living (e.g., getting up from a sitting position, bending over, going up and down stairs etc.); The score is then normalized on a 0-100 scale. Higher values indicate a worse outcome

  12 months

Secondary Outcomes (14)

• Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)

  baseline, 2,6,24 months

• IKDC-Subjective Score

  baseline, 2,6,12,24 months

• IKDC-Objective Score (Objective International Knee Documentation Committee)

  baseline, 2,6,12,24 months

• Patient Acceptable Symptom State (PASS)

  baseline, 2,6,12,24 months

• EuroQol Visual Analogue Scale (EQ-VAS)

  baseline, 2,6,12,24 months

Study Arms (2)

MFAT + HA left knee - MFAT + placebo right knee

EXPERIMENTAL

The left knee will be treated with an injection of high-molecular-weight hyaluronic acid (4 cc) and microfragmented autologous adipose tissue (6 cc), harvested from the abdominal site.The right knee will be treated with microfragmented autologous adipose tissue (6 cc), also harvested from the abdominal site by liposuction and microfragmentation, combined with an injection of 4 cc of saline (NaCl 0.9%)

Device: MFAT + HA left knee - MFAT + placebo right knee

MFAT + HA right knee - MFAT + placebo left knee

ACTIVE COMPARATOR

The right knee will be treated with an injection of high-molecular-weight hyaluronic acid (4 cc) and microfragmented autologous adipose tissue (6 cc), harvested from the abdominal site.The left knee will be treated with microfragmented autologous adipose tissue (6 cc), also harvested from the abdominal site by liposuction and microfragmentation, combined with an injection of 4 cc of saline (NaCl 0.9%)

Biological: MFAT + HA right knee - MFAT + placebo left knee

Interventions

MFAT + HA left knee - MFAT + placebo right knee DEVICE

The left knee will be treated with an injection of high-molecular-weight hyaluronic acid (4 cc) and microfragmented autologous adipose tissue (6 cc), harvested from the abdominal site.The right knee will be treated with microfragmented autologous adipose tissue (6 cc), also harvested from the abdominal site by liposuction and microfragmentation, combined with an injection of 4 cc of saline (NaCl 0.9%)

MFAT + HA left knee - MFAT + placebo right knee

MFAT + HA right knee - MFAT + placebo left knee BIOLOGICAL

The right knee will be treated with an injection of high-molecular-weight hyaluronic acid (4 cc) and microfragmented autologous adipose tissue (6 cc), harvested from the abdominal site.The left knee will be treated with microfragmented autologous adipose tissue (6 cc), also harvested from the abdominal site by liposuction and microfragmentation, combined with an injection of 4 cc of saline (NaCl 0.9%)

MFAT + HA right knee - MFAT + placebo left knee

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged between 18 and 75;
• Radiographic evidence of bilateral OA of the knees graded between 2 and 4 on the Kellgren-Lawrence scale;
• Pain equal to or greater than 4 on the Numeric Rating Scale (NRS) for both knees;
• Failure, defined as persistence of symptoms after at least 6 months of conservative treatment (pharmacological, physiotherapy, or infiltration treatment);
• Ability and willingness to undergo the study procedures and comply with the instructions given by the study team; 6. No history of
• \. Failure, defined as persistent symptoms, after at least 6 months of conservative treatment (pharmacological, physiotherapy, or infiltration treatment); 5. Ability and consent of patients to actively participate in the rehabilitation and follow-up protocol; 6. Signature of informed consent

You may not qualify if:

• Patients incapable of understanding and willing;
• Diagnosis of active neoplasia;
• Diagnosis of rheumatoid arthritis, Reiter's syndrome, psoriatic arthritis, gout, ankylosing spondylitis, or arthritis resulting from another inflammatory disease; human immunodeficiency virus (HIV) infection, active viral hepatitis; chondrocalcinosis;
• Patients with uncontrolled diabetes mellitus;
• Patients with uncontrolled thyroid metabolic disorders;
• Patients who abuse alcohol, drugs, or medications;
• Patients with lower limb misalignment greater than 5°;
• Body Mass Index \> 35 kg/m2;
• Pregnancy or breastfeeding, or plans to become pregnant during the study period .
• Patients with a history of trauma or intra-articular infiltration of therapeutic substances in the 6 months prior to screening.
• Patients who have undergone knee surgery in the 12 months prior to screening.
• Patients with insufficient abdominal adipose tissue, as assessed by the investigator.

Sponsors & Collaborators

• Istituto Ortopedico Rizzoli: lead

Study Sites (1)

IRCCS Istituto Ortopedico Rizzoli

Bologna, 40127, Italy

RECRUITING

Related Publications (19)

• 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.

  PMID: 38727286 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.

  PMID: 23051701 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.

  PMID: 20444320 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.

  PMID: 26240572 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.

  PMID: 27006923 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.

  PMID: 23914338 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.

  PMID: 33464397 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.

  PMID: 36104484 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.

  PMID: 30255987 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.

  PMID: 31146351 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.

  PMID: 21736710 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.

  PMID: 35984721 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.

  PMID: 38202074 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.

  PMID: 38037038 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.

  PMID: 38022237 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.

  PMID: 28801676 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.

  PMID: 29967404 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.

  PMID: 17825587 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.

  PMID: 25581339 BACKGROUND

MeSH Terms

Conditions

Osteoarthritis

Interventions

long-chain-alcohol O-fatty-acyltransferase

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• Alessandro Di Martino, MD

  Istituto Ortopedico Rizzoli - II Clinica Ortopedica e Traumatologica

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alessandro Di Martino, MD

CONTACT

0516366567; alessandro.dimartino@ior.it

Roberta Licciardi, MsC

CONTACT

0516366567; roberta.licciard@ior.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The patient will not be aware of the side where hyaluronic acid will also be injected in addition to the microfragmented adipose tissue Clinical evaluations will be performed by medical personnel other than those who have performed the surgical and infiltrative procedures
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomized controlled double-blind parallel-arm study with 1:1 allocation

Study Record Dates

• First Submitted: August 6, 2025
• First Posted: August 13, 2025
• Study Start: September 29, 2025
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2030
• Last Updated: December 3, 2025

Record last verified: 2025-12

Locations

IT (1)