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

Official title

Randomized Double- Blind Study on the 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. Double-Blind Randomized Controlled Clinical Trial

Overview

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.

Detailed description

100 patients with symptomatic bilateral knee OA will be included in a randomized controlled double-blind study in which the clinical outcomes of treating OA with microfragmented autologous adipose tissue associated with high-molecular-weight hyaluronic acid versus treatment with microfragmented autologous adipose tissue will be evaluated and compared. One 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 contralateral knee will be treated with microfragmented autologous adipose tissue (6 cc), also harvested from the abdominal site by liposuction and microfragmentation, combining an injection of 4 cc of saline (NaCl 0.9%) to make the volume of product injected into both knees equal. During screening, the eligibility of potentially enrollable subjects will be assessed.Once they are deemed eligible, the baseline visit will be performed, which will take place in the divisional or research clinic.

This will include: - the presentation of the study, the collection of informed consents and the administration and collection of subjective and objective evaluation questionnaires by medical staff. Patients will be clinically evaluated at 0-2-6-12 and 24 months follow-up

Interventions

• Device MFAT + HA left knee - MFAT + placebo right knee
  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%)
• Biological MFAT + HA right knee - MFAT + placebo left knee
  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%)

Primary outcome measures

• Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [Time frame: 12 months]

Secondary outcome measures (12)

• Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [Time frame: baseline, 2,6,24 months]
• IKDC-Subjective Score [Time frame: baseline, 2,6,12,24 months]
• IKDC-Objective Score (Objective International Knee Documentation Committee) [Time frame: baseline, 2,6,12,24 months]
• Patient Acceptable Symptom State (PASS) [Time frame: baseline, 2,6,12,24 months]
• EuroQol Visual Analogue Scale (EQ-VAS) [Time frame: baseline, 2,6,12,24 months]
• Functional Numerical Rating Scale (NRS -functional) [Time frame: baseline, 2,6,12,24 months]
• Numerical Rating Scale (NRS - pain) [Time frame: baseline, 2,6,12,24 months]
• Objective parameters- Range of Motion [Time frame: baseline, 2,6,12,24 months]
• Objective parameters - Circumferences [Time frame: baseline, 2,6,12,24 months]
• Patient expectations regarding treatment [Time frame: baseline]
• Opinion on the treatment [Time frame: 6,12,24 months]
• Effectiveness of the blinding procedure [Time frame: baseline]

Eligibility criteria

Inclusion criteria

• 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

4\. 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

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Italy · 1 center

• IRCCS Istituto Ortopedico Rizzoli — Bologna

Publications

• 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
• 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
• 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
• 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
• 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
• 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
• 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- PMID 33464397
• 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/s00167-0 PMID 36104484

Identifiers

NCT: NCT07121556 · HYALOFAT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗