Osteoarthritis
Conditions
Keywords
mesenchymal stem cells, stem cells, Stromal Vascular Fraction, Osteoarthritis
Brief summary
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.
Detailed description
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.
Interventions
DEVICEStromal 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 transferred at least 30 times from one syringe to the other. Syringe content is again centrifugated for 4 minutes. The oil is discarded and approximately 1.5ml SVF fraction remains.
PROCEDUREPlattelet 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
Sponsors
Adrien Schwitzguebel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
This study is triple-blinded concerning (i) the participants during the intervention and throughout the study duration, (ii) the outcome assessor, and (iii) the statistician. The investigator in charge of the injections will be unblinded and therefore will not be assigned to outcomes assessment. Follow-up and outcome assessment will be identical for both arms.
Intervention model description
Multicentric randomized. Randomization will be performed at a 1:1 ratio to either the intervention arm or the active comparator. Each block of 4 patients will be assigned to specific strata according to age (over or under 40), presence of either partial, full cartilage defects or full cartilage defects with bone deformation.
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| WOMAC | 6 months | Functional improvement measured with the 0%-100% normalized Western Ontario McMaster Universities Osteoarthritis Index, where 0% indicates complete absence of symptoms and 100% indicates maximal possible symptoms severity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MOCART | 6 months, 12 months | The absolute difference (changes from baseline to other time points) between the treatment and control arms on Magnetic Resonance Observation of Cartilage Repair Tissue score. (0 = poor cartilage repair, 100 complete and normal cartilage repair) |
| VAS | 1, 2, 3, 6, and 12 months | The absolute difference (changes from baseline to other time points) in pain Visual Analogue Scale (VAS) during maximal physical activity performed by the patient, between the treatment and control arms on a 0 to 10 scale. 0: no pain, 10: maximal pain |
| WOMAC | 1, 2, 3, 6, and 12 months | The absolute difference (changes from baseline to other time points) between the treatment and control arms on the Western Ontario McMaster Universities Osteoarthritis Index on knee osteoarthritis cases. From 0 to 100, being 0: no limitation, 100: extreme limitation |
| Return to work | 1, 2, 3, 6, and 12 months | The absolute difference between the treatment and control arms on length of time to return work in days |
| Return to sport | 1, 2, 3, 6, and 12 months | The absolute difference between the treatment and control arms on length of time to return to sports in days |
| AMADEUS SCORE | 6 and 12 moths | The absolute difference (changes from baseline to other time points) between the treatment and control arms on Affected cartilage quality on MRI using Area Measurement And Depth Underlying Structures (AMADEUS) score. (0 worst, 100 best) |
| WORMS | 6 Months, 12 months | The absolute difference (changes from baseline to other time points) between the treatment and control arms on Whole-Organ Magnetic Resonance Imaging Score score. (0 normal structure, 332 most severe grade). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Numer of current and previous treatments | Baseline | Number of current and previous treatments for osteoarthritis and tendinopathy |
| Kellgren-Lawrence | Baseline | Baseline Kellgren-Lawrence grade in case of osteoarthritis. I: Mild to IV: Severe |
| Number of patients with post-traumatic osteoarthritis | Baseline | Number of patients with post-traumatic osteoarthritis |
| Age | Baseline | Age |
| Sex | Baseline | Sex |
| Height | Baseline | Height, cm |
| Weight | Baseline | Weight, kg |
| BMI | Baseline | BMI |
| Number of patients with tobacco use | Baseline | Number of patients with tobacco use |
| Number of Participants with concomitant diseases | Baseline | Number of Participants with concomitant diseases (diabetes Miletus, dyslipidemia, arterial hypertension, osteopenia, osteoporosis, presence of rheumatologic disease, renal failure, and other relevant comorbidity) |
Contacts
Primary ContactAdrien Schwitzguébel, MD.
Outcome results
None listed