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

NCT ID: NCT07121556

Last Updated: 2025-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-09-29

Study Completion Date

2030-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Osteoarthritis Knees Both

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is a randomized controlled double-blind parallel-arm study with 1:1 allocation
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
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

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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%)

Group Type ACTIVE_COMPARATOR

MFAT + HA right knee - MFAT + placebo left knee

Intervention Type 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 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%)

Group Type EXPERIMENTAL

MFAT + HA left knee - MFAT + placebo right knee

Intervention Type 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%)

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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%)

Intervention Type DEVICE

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%)

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Male or female patients aged between 18 and 75;
2. Radiographic evidence of bilateral OA of the knees graded between 2 and 4 on the Kellgren-Lawrence scale;
3. Pain equal to or greater than 4 on the Numeric Rating Scale (NRS) for both knees;
4. Failure, defined as persistence of symptoms after at least 6 months of conservative treatment (pharmacological, physiotherapy, or infiltration treatment);
5. 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

1. Patients incapable of understanding and willing;
2. Diagnosis of active neoplasia;
3. 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;
4. Patients with uncontrolled diabetes mellitus;
5. Patients with uncontrolled thyroid metabolic disorders;
6. Patients who abuse alcohol, drugs, or medications;
7. Patients with lower limb misalignment greater than 5°;
8. Body Mass Index \> 35 kg/m2;
9. Pregnancy or breastfeeding, or plans to become pregnant during the study period .
10. Patients with a history of trauma or intra-articular infiltration of therapeutic substances in the 6 months prior to screening.
11. Patients who have undergone knee surgery in the 12 months prior to screening.
12. Patients with insufficient abdominal adipose tissue, as assessed by the investigator.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Istituto Ortopedico Rizzoli

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Alessandro Di Martino, MD

Role: PRINCIPAL_INVESTIGATOR

Istituto Ortopedico Rizzoli - II Clinica Ortopedica e Traumatologica

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

IRCCS Istituto Ortopedico Rizzoli

Bologna, , Italy

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Italy

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Alessandro Di Martino, MD

Role: CONTACT

0516366567

Roberta Licciardi, MsC

Role: CONTACT

0516366567

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Alessandro Di Martino, MD

Role: primary

0516366567

Roberta Licciardi, MsC

Role: backup

0516366567

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 25581339 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 38727286 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23051701 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20444320 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26240572 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27006923 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23914338 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33464397 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36104484 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30255987 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31146351 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21736710 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35984721 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 38202074 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 38037038 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 38022237 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28801676 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29967404 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17825587 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

HYALOFAT

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.