Effectiveness of Stromal Vascular Fraction (SVF) and Platelet -Rich Plasma (PRP) in Patients With Knee Osteoarthritis: Study Protocol for a Phase III, Prospective, Randomized, Controlled Multi-center Study.

Effectiveness of Stromal Vascular Fraction (SVF) and Platelet -Rich Plasma (PRP) in Patients With Knee Osteoarthritis: Study Protocol for a Phase III, Prospective, Randomized, Controlled Multi-center Study : (SPOST Study)

This multicenter, randomized, triple-blind, controlled trial, will enroll 108 patients who will block-randomized in a 1:1 ratio to either the intervention or control group. The main question to answer are the clinical efficacy of SVF as adjuvant therapy to PRP on functionality and tissue regeneration for knee osteoarthritis.

Background:

Osteoarthritis, the most common joint disease, has a high social and individual impact and the development of therapeutic options is a public health priority. It's multifactorial etiology is still a source of active research

Most common conservative treatments for osteoarthritis treatment include painkillers, active physical therapies, orthotics, infiltrations of corticosteroids, hyaluronic acid (HA), and platelet-rich plasma (PRP).

PRP may be beneficial in osteoarthritis by interfering with catabolic and inflammatory events and by subsequently promoting anabolic responses. Activation of PRP releases biologically active components, including platelet-derived growth factor (PDGF), transforming growth factor-β (PGF-β), type I insulin-like growth factor (IGF-1) and vascular endothelial growth factor (VEGF). These proteins are responsible for a range of critical tissue healing roles such as chondrocyte and mesenchymal stem cells proliferation, bone and vessel remodelling, inflammatory modulation and collagen synthesis.

For osteoarthritis, an improvement of clinical outcomes has been found in several clinical trials, presumably associated with the chondroprotective effect of PRP. Nevertheless, an in-vivo effect on human cartilage regeneration is not yet demonstrated despite the numerous studies approaching the subject.

Preclinical models elucidated how injected Adipose Derived- Mesenchymal Stem Cells (AD-MSC) coordinate the cartilage regeneration process through paracrine mechanisms, producing cytokines and trophic bioactive factors that stimulate cellular proliferation, reduce inflammation, fibrosis, oxidative stress, and chondrocytes senescence.

Stromal Vascular Fraction (SVF), a product from specific adipose tissue processing, contains mesenchymal stem cells, endothelial precursor cells, T regulatory cells, macrophages, smooth muscle cells, pericytes and preadipocytes. SVF extraction and injection techniques have been recently used as an alternative to harvest AD-MSC due to its logistic simplicity and feasibility in clinical practice.

SVF injections produce a clinically significant effect on the treatment of knee osteoarthritis, and a possible improvement in cartilage quality.

This clinical trial aims to assess the clinical efficacy of SVF as adjuvant therapy to PRP on functionality and tissue regeneration on osteoarthritis.

Inclusion Criteria:

• Informed Consent as documented by signature (Appendix Informed Consent Form)
• Age older than 16 years old,
• Symptomatic knee osteoarthritis confirmed by magnetic resonance imaging (MRI)
• Absence of free or displaced meniscal or cartilage fragments on the MRI of the affected knee
• Failure of first-line conservative management in the last 3 months including medical or infiltrative treatment, orthotics use, active rehabilitation plan, adaptation of sports and work habits.

Exclusion Criteria:

• Patient is familiar with the lipoaspiration process
• Significant disease of the contralateral member with a function evaluated with SANE score below 80%
• Microcristalline disease (i.e. gout, pseudogout),
• Active inflammatory rheumatic disorders,
• Need of regular anti-inflammatory treatment (either NSAIDs or corticosteroids),
• Allergy to local anesthetics or epinephrin
• Bleeding disorders or current anticoagulation therapy
• Patients with decompensated renal failure, hepatic dysfunction, or severe pulmonary or cardiovascular disease,
• Patients with an immunocompromised status
• Women who are pregnant or intend to become pregnant during the study
• Inability to follow the procedures of the study, e.g., due to language problems, psychological disorders, dementia, etc. of the participant,
• Known or suspected non-compliance, drug, or alcohol abuse
• Previous enrollment into the current study,
• Participation in another study with investigational drug or procedure within the 30 days preceding and during the present study
• Enrollment of the investigator, his/her family members, employees, and other dependent persons

If a bilateral disease is present and both sides require either the experimental or the control intervention, only the most symptomatic side will be studied.