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

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

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.

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

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.