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.

Официальное название

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)

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство Stromal Vascular Fraction infiltration
  Procedure to prepare SVF: In the operations room and after aseptic technic, local anesthesia is applied in the liposuction incision site with lidocaine 1% without epinephrine subcutaneously. 60 ml of tumescent solution are injected. After 15-20 minutes waiting, 15 ml of lipoaspiration per side are recollected into a double syringe. This is centrifuged for 4 minutes at 2.500 rpm and the remaining fat is separated from the other fractions. Two 1.4 mm GEMS syringes are attached together, and fat is
• Процедура Plattelet Rich Plasma infiltration
  Procedure to prepare PRP: 15 cm of peripheral blood obtained by venipuncture are centrifugated at 1500 RPM during 5 minutes. Using PRP Arthrex kit platelets poor plasma is discarded and 1-3 mm of PRP are ready to be injected

Первичные конечные точки

• WOMAC [Срок оценки: 6 months]

Вторичные конечные точки (7)

• VAS [Срок оценки: 1, 2, 3, 6, and 12 months]
• WOMAC [Срок оценки: 1, 2, 3, 6, and 12 months]
• Return to work [Срок оценки: 1, 2, 3, 6, and 12 months]
• Return to sport [Срок оценки: 1, 2, 3, 6, and 12 months]
• AMADEUS SCORE [Срок оценки: 6 and 12 moths]
• WORMS [Срок оценки: 6 Months, 12 months]
• MOCART [Срок оценки: 6 months, 12 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• World Medical A. WMA declaration of Helsinki : ethical principles for medical research involving human subjects 2013. First edition. ed. Guildford, Surrey: Canary Publications; 2014. 12 pages p.
• Harmonization ICo. Guideline for Good Clinical Practice. 1996.
• McCormack J, Underwood F, Slaven E, Cappaert T. THE MINIMUM CLINICALLY IMPORTANT DIFFERENCE ON THE VISA-A AND LEFS FOR PATIENTS WITH INSERTIONAL ACHILLES TENDINOPATHY. Int J Sports Phys Ther. 2015 Oct;10(5):639-44. PMID 26491614
• Franchignoni F, Vercelli S, Giordano A, Sartorio F, Bravini E, Ferriero G. Minimal clinically important difference of the disabilities of the arm, shoulder and hand outcome measure (DASH) and its shortened version (QuickDASH). J Orthop Sports Phys Ther. 2014 Jan;44(1):30-9. doi: 10.2519/jospt.2014.4893. Epub 2013 Oct 30. PMID 24175606
• Emanuel EJ, Wendler D, Grady C. What makes clinical research ethical? JAMA. 2000 May 24-31;283(20):2701-11. doi: 10.1001/jama.283.20.2701. PMID 10819955
• Agarwal N, Mak C, Bojanic C, To K, Khan W. Meta-Analysis of Adipose Tissue Derived Cell-Based Therapy for the Treatment of Knee Osteoarthritis. Cells. 2021 Jun 1;10(6):1365. doi: 10.3390/cells10061365. PMID 34206010
• Ma W, Liu C, Wang S, Xu H, Sun H, Fan X. Efficacy and safety of intra-articular injection of mesenchymal stem cells in the treatment of knee osteoarthritis: A systematic review and meta-analysis. Medicine (Baltimore). 2020 Dec 4;99(49):e23343. doi: 10.1097/MD.0000000000023343. PMID 33285713
• Zhao D, Pan JK, Yang WY, Han YH, Zeng LF, Liang GH, Liu J. Intra-Articular Injections of Platelet-Rich Plasma, Adipose Mesenchymal Stem Cells, and Bone Marrow Mesenchymal Stem Cells Associated With Better Outcomes Than Hyaluronic Acid and Saline in Knee Osteoarthritis: A Systematic Review and Network Meta-analysis. Arthroscopy. 2021 Jul;37(7):2298-2314.e10. doi: 10.1016/j.arthro.2021.02.045. Epub PMID 33713757

Идентификаторы

NCT: NCT05660824 · 28.12.2024

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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