Treatment of osteoarthritis with autologous, micro-fragmented adipose tissue: a study protocol for a randomized controlled trial
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ABSTRACT: Background
Osteoarthritis is a destructive joint disease that leads to degeneration of cartilage and other morphological changes in the joint. No medical treatment currently exists that can reverse these morphological changes. Intra-articular injection with autologous, micro-fragmented adipose tissue has been suggested to relieve symptoms. Methods/Design
The study is a blinded randomized controlled trial with patients allocated in a 1:1 ratio to 2 parallel groups. Patients suffering from pain and functional impairment due to osteoarthritis Kellgren-Lawrence grades 2–3 in the tibiofemoral joint are eligible for inclusion. The intervention group is treated with an intra-articular injection with autologous, micro-fragmented adipose tissue prepared using the Lipogems® system. The control group receives an intra-articular injection with isotonic saline. In total, 120 patients are to be included. The primary outcome is The Knee injury and Osteoarthritis Outcome Score (KOOS4) evaluated at 6 months. Secondary outcomes are KOOS at 3, 12 and 24 months; the Tegner activity score; treatment failure; and work status of the patient. The analysis will be conducted both as intention-to-treat and per-protocol analysis. Discussion
This trial is the first to investigate the efficacy of autologous, micro-fragmented adipose tissue in a randomized controlled trial. The study uses the patient-reported outcome measure Knee Injury and Osteoarthritis Outcome Score (KOOS4) after 6 months as the primary outcome, as it is believed to be a valid measure to assess the patient’s opinion about their knee and associated problems when suffering from osteoarthritis.
SUBMITTER: Mikkelsen R
PROVIDER: S-EPMC8549306 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundChondral lesions of the knee represent a challenge for the orthopaedic surgeon. Several treatments have been proposed with variable success rate. Recently, new therapeutic approaches, such as the use of mesenchymal stem cells, have shown promising results. The adipose tissue is a good source of these naturally occurring regenerative cells, due to its abundance and easy access. In addition, it can be used to provide cushioning and filling of structural defects. The 1-year safety and outcome of a single intra-articular injection of autologous and micro-fragmented adipose tissue in 30 patients affected by diffuse degenerative chondral lesions was evaluated.MethodsMicro-fragmented adipose tissue was obtained using a minimal manipulation technique in a closed system. The safety of the procedure was evaluated by recording type and incidence of any adverse event. The clinical outcomes were determined using the KOOS, IKDC-subjective, Tegner Lysholm Knee, and VAS pain scales taken pre-operatively and at 12 months follow-up. A level of at least 10 points of improvement in the scores has been selected as cut-off representing a clinically significant difference.ResultsNo relevant complications nor clinical worsening were recorded. A total median improvement of 20 points has been observed in IKDC-subjective and total KOOS, and a higher percentage of success was found in VAS pain and Tegner Lysholm Knee, where the total median improvement was 24 and 31 points, respectively.ConclusionThe results of this study show the safety and feasibility of using autologous and micro-fragmented adipose tissue in patients affected by diffuse degenerative chondral lesions. The technique is safe, minimally invasive, simple, one-step, with low percentage of complications, and compliant with the regulatory panorama.
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Project description:BACKGROUND:The diabetic foot ulcer (DFU) is one of the most prevalent complications of diabetes mellitus and often develops severe effects that can lead to amputation. A non-healing "minor" amputation often precedes a major amputation resulting in a negative impact on the function and quality of life of the patients. Stem cell-based therapies have emerged as a promising option to improve healing, and the adipose tissue is an abundant and easy to access source. The injection of autologous micro-fragmented adipose tissue at the amputation stump of a diabetic population undergoing a lower limb minor amputation was evaluated and compared with the standard care. METHODS:In this randomized controlled trial with two arms (parallel assignment) and no masking, 114 patients undergoing a lower limb minor amputation were randomized to standard of care or to micro-fragmented adipose tissue injection prepared using a minimal manipulation technique (Lipogems®) in a closed system. Clinical outcomes were determined monthly up to 6?months. Primary endpoint of the study was the evaluation of the healing rate and time after the minor amputation. Secondary endpoints included the assessment of safety, feasibility, technical success, relapse rate, skin tropism, and intensity of pain. RESULTS:At 6?months, 80% of the micro-fragmented adipose tissue-treated feet healed and 20% failed as compared with the control group where 46% healed and 54% failed (p?=?0.0064). No treatment-related adverse events nor relapses were documented, and technical success was achieved in all cases. The skin tropism was improved in the treatment group, and the pain scale did not differ between the two groups. CONCLUSION:The results of this randomized controlled trial suggest that the local injection of autologous micro-fragmented adipose tissue is a safe and valid therapeutic option able to improve healing rate following minor amputations of irreversible DFU. The technique overcomes several stem cell therapy-related criticisms and its potential in wound care should be better evaluated and the therapeutic indications could be expanded. TRIAL REGISTRATION:ClinicalTrials.gov number: NCT03276312. Date of registration: September 8, 2017 (retrospectively registered).
| S-EPMC6664586 | biostudies-literature
Project description:The study aimed to evaluate the short-term clinical effect, therapeutic response rate (TRR%), and therapy safety of a single intra-articular autologous MFAT injection for symptomatic knee OA. Secondly, patient- and pathology-related parameters were investigated to tighten patient selection for MFAT therapy. Sixty-four subjects with symptomatic mild-severe knee OA were enrolled in a single-center trial and received a unilateral (n = 37) or bilateral (n = 27) MFAT injection. After liposuction, the adipose tissue was mechanically processed with the Lipogem® device, which eventually produced 8-10 cc of MFAT. Subjects were clinically assessed by means of the KOOS, NRS, UCLA, and EQ-5D at baseline and 1, 3, 6, and 12 months after injection. Adverse events were recorded at each follow-up timepoint. The TRR was defined according to the OMERACT-OARSI criteria and baseline MRI was scored following the MOAKS classification. The TRR of the index knee was 64% at 3 months and 45% at 12 months after injection. Therapy responders at 12 months improved with 28.3 ± 11.4 on KOOS pain, while non-responders lost -2.1 ± 11.2 points. All clinical scores, except the UCLA, improved significantly at follow-up compared to baseline (p < 0.05). In the bilateral cohort, no difference in baseline scores or TRR was found between the index knee and contralateral knee (n.s.). An inflammatory reaction was reported in 79% of knees and resolved spontaneously within 16.6 ± 13.5 days after MFAT administration. Numerous bone marrow lesions (BML) were negatively correlated with the TRR at 12 months (p = 0.003). The study demonstrated an early clinical improvement but a mediocre response rate of 45% at 12 months after a single intra-articular injection with autologous MFAT. Assessment of bone marrow lesions on MRI can be helpful to increase the therapeutic responsiveness of MFAT up to 70% at 12 months. In comparison to repetitive injection therapies such as cortisone, hyaluronic acid, and PRP, administration of MFAT might become a relevant alternative in well-selected patients with symptomatic knee OA.
| S-EPMC8196751 | biostudies-literature
Project description:Similar to the disease affecting humans, osteoarthritis (OA) is a painful musculoskeletal condition affecting 20% of the adult canine population. Several solutions have been proposed, but the results achieved to date are far from being satisfactory. New approaches, such as intra-articular delivery of cells (including mesenchymal stromal cells), have been proposed. Among the many sources, the adipose tissue is considered very promising. We evaluated the safety, feasibility, and efficacy of a single intra-articular injection of autologous and micro-fragmented adipose tissue (MFAT) in 130 dogs with spontaneous OA. MFAT was obtained using a minimally invasive technique in a closed system and injected in the intra- and/or peri-articular space. Clinical outcomes were determined using orthopedic examination and owners' scores for up to 6 months. In 78% of the dogs, improvement in the orthopedic score was registered 1 month after treatment and continued gradually up to 6 months when 88% of the dogs improved, 11% did not change, and 1% worsened compared with baseline. Considering the owners' scores at 6 months, 92% of the dogs significantly improved, 6% improved only slightly, and 2% worsened compared with baseline. No local or systemic major adverse effects were recorded. The results of this study suggest that MFAT injection in dogs with OA is safe, feasible, and beneficial. The procedure is time sparing and cost-effective. Post injection cytological investigation, together with the clinical evidence, suggests a long-term pain control role of this treatment. The spontaneous OA dog model has a key role in developing successful treatments for translational medicine. Stem Cells Translational Medicine 2018;7:819-828.
| S-EPMC6216453 | biostudies-literature
Project description:BackgroundAdipose tissue has recently gained growing interest in the treatment of osteoarthritis (OA). The aim of the present study was to evaluate the efficacy of a single injection of autologous micro-fragmented adipose tissue (aMFAT) associated with arthroscopy (cartilage debridement/meniscal regularization or selective meniscectomy/micro-drilling) for symptomatic knee OA.MethodsThis retrospective, single-center study included 49 patients (50 knees) affected by knee OA (radiographic Kellgren-Lawrence III-IV) treated with a single injection of autologous micro-fragmented adipose tissue and knee arthroscopy. Knee Injury and Osteoarthritis Outcome Score (KOOS) and subjective International Knee Documentation Committee (IKDC) score were the primary outcome measures and were collected at one and 2 years post-operatively. Patients were divided into clusters based on age, complexity of arthroscopic procedures and chondral lesion grade.ResultsFour patients underwent knee replacement (8%). No major adverse events were reported. Minimal Clinically Important Difference (MCID) for KOOS and IKDC was reached by 84 and 74% of all cases at 1 year and by 80 and 76% at 2 years, respectively. High grade chondral lesions negatively affected the outcome at 2 years follow-up (p < 0.05 for IKDC, KOOS overall and 3 out of 5 subscales).ConclusionThe injection of micro-fragmented adipose tissue associated with arthroscopy demonstrated to be a safe and effective procedure for the treatment of knee OA, with a substantial improvement in IKDC and KOOS scores and without major complications.
| S-EPMC9641752 | biostudies-literature
Project description:BACKGROUND:The social impact of degenerative diseases is steadily increasing, because of the continued rise in the mean age of the active population. Articular cartilage lesions are generally associated with disability and symptoms such as joint pain and reduced function, and remain a challenge for the orthopaedic surgeon. Several non-invasive solution have been proposed, but the results achieved to date are far from being completely satisfactory. Recently, new therapeutic approaches, such as the use of mesenchymal stem cells, have been developed. Among the many sources, the adipose tissue is nowadays considered one of the smartest, due to its abundance and easy access. The aim of this retrospective study is to explore whether patients affected by symptomatic knee osteoarthritis treated with micro-fragmented adipose tissue associated with a chondral shaving procedure experience an improvement in symptoms and function. METHODS:Thirty-eight patients affected by symptomatic knee osteoarthritis were treated in 2015 with an arthroscopic procedure associated with an injection of autologous and micro-fragmented adipose tissue. Micro-fragmented adipose tissue was obtained using a minimal manipulation technique in a closed system. Clinical outcomes were determined at 1, 3, 6, and 12 months follow-up using Knee Injury and Osteoarthritis Outcome Score questionnaire and direct physical examination. Safety of the procedure, recording type and incidence of any adverse event, was also assessed. RESULTS:A steady and statistically significant improvement of all the clinical scores from pre-operative evaluation to 1, 3, 6, and 12 months follow-up was observed, with KOOS sport and quality of life being the most improved scores. On average, 92% of the patients clinically improved and 100% of them were satisfied with the treatment. No adverse events nor relevant complications were recorded. CONCLUSION:The result of the study pointed to micro-fragmented adipose tissue as a safe and beneficial adjuvant in the surgical treatment of degenerative knee chondropathy. The procedure is simple, sustainable, quick, minimally invasive, one-step, and safe. After one year, the results are very satisfactory and promising. A longer follow-up is needed to draw definitive conclusions and enlarge the indications. TRIAL REGISTRATION:Registered at clinicaltrials.gov as NCT03527693 on 27 April 2018 (retrospectively registered).
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Project description:BackgroundKnee osteoarthritis (OA) is a common, chronic, progressive and degenerative disease which affects patients' quality of life and may cause disability and social isolation. OA is a huge economic burden for the patient and a large strain for the whole healthcare system. Articular cartilage has a small potential to repair, with progressively more clinicians emphasizing cellular therapy. Subcutaneous fat tissue in human body is a large reservoir of mesenchymal stem cells (MSCs) and is been harvested in minimally invasive, simple procedure. Up to date there is no prospective randomized controlled studies demonstrating effectiveness and role of adipose tissue injections in OA treatment. The purpose of this study is to assess functional and clinical changes among patients with symptomatic knee OA treated with intra-articular injections of autologous adipose tissue or platelet rich plasma (PRP) and to compare efficacy of both therapeutic methods.MethodsThis is a prospective, randomized, controlled study. Patients who meet inclusion criteria will be allocated to Fat Tissue group or PRP group randomly. Subjects will receive an intra articular injection with autologous adipose tissue and PRP respectively. Patients will be assessed five times: before treatment and 1, 3, 6 and 12 months after the treatment. The assessment consists of patient reported outcome measures (The Knee injury and Osteoarthritis Outcome Score, International Knee Documentation Committee 2000, the Western Ontario and McMaster Universities Osteoarthritis Index, the Health Questionnaire EQ- 5D- 5 L), three functional tests (The Timed Up and Go Test, The 5 Times Sit to Stand Test, The 10 m Walk Test) and Maximal Isometric Voluntary Contraction.DiscussionThis study protocol has several strengths and weaknesses. One of strongest point of this study is the wide, multidimensional functional assessment which will give a large amount of objective data. On the other hand, lack of blinding has to be considered as a risk of both subject and investigator bias.Trial registrationname of registry: ClinicalTrials.gov, trial registration number: NCT04321629, retrospectively registered on date of registration.
| S-EPMC7240999 | biostudies-literature
Project description:BackgroundThe objective of this study is to analyze the influence of a 14-week periodized circuit training protocol on patients with knee osteoarthritis (OA), in randomized intervention groups, on thigh intermuscular adipose tissue (interMAT), body composition, systemic inflammation, cartilage degradation, and its repercussion on pain, functional performance and quality of life.MethodsThis study presents a protocol for a randomized controlled trial. Sixty selected participants diagnosed with knee OA grades II and III, 40-65 years old and BMI < 30 kg/m2, will be randomly divided into three groups:periodized circuit training, strength training, and educational protocol. The circuit training and strength training protocols consist of 14-week training protocols conducted 3 times a week. The circuit training group will perform selected exercises previously stratified as light, moderate, and intense, arranged progressively in a circuit model, the strength group will perform regular strength exercises, and the educational protocol group will participate in a 14-week protocol with lectures twice a month about healthy lifestyles. Baseline and follow-up evaluations will be conducted for thigh interMAT (computed tomography), body composition (DXA), inflammation (IL-1β, IL-6, IL-10, TNF-α, leptin, and adiponectin), and joint degradation biomarkers (uCTX-II and sCOMP), performance-based tests (30s Chair Stand Test, 40 m Fast-paced Walk Test and Stair Climb Test), quadriceps and hamstring maximal isometric voluntary contraction (MIVC), and questionnaires (WOMAC and pain catastrophizing scale). Repeated measures ANOVA will be used to compare differences between groups (circuit training X strength training X educational protocol) at the different times of assessment (baseline x follow-up or baseline x during protocol x follow-up) for each of the dependent variables. When significant main effects were found, the pots hoc Bonferroni test will be used to identify statistical differences. A significance level of 5% (p < 0.05) will be adopted.DiscussionThis will be the first randomized controlled trial to assess the effects of a circuit training protocol on patients with knee OA on thigh intermuscular adipose tissue (interMAT). Given the prevalence and impact of OA and the widespread availability of this intervention, assessing the efficacy of a low-cost, non-pharmacological, and non-invasive treatment for knee OA patients has the potential for immediate and high clinical impact.Trial registrationClinicalTrials.gov, NCT02761590 , registered in May 4, 2016.
| S-EPMC6267088 | biostudies-literature
Project description:Mesenchymal stem cells (MSCs) have been the focus of an emerging treatment for osteoarthritis. However, few studies reported about outcomes of an intra-articular injection of autologous adipose-derived mesenchymal stem cells (AD-MSCs). This study aimed to assess the efficacy and safety of a single intra-articular injection of AD-MSCs for patients with knee osteoarthritis. It was a prospective double-blinded, randomized controlled, phase IIb clinical trial. AD-MSCs were administered for 12 patients (MSC group), and the group was compared with 12 knees with injection of normal saline (control group) up to 6 months. All procedures were performed in the outpatient clinic. Primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) score. Secondary outcome measure included various clinical and radiologic examination, and safety after injection. Change of cartilage defect after injection was evaluated using magnetic resonance imaging (MRI). Single injection of AD-MSCs led to a significant improvement of the WOMAC score at 6 months. In the control group, there was no significant change in the WOMAC score at 6 months. No serious adverse events were observed in both groups during the follow-up period. In MRI, there was no significant change of cartilage defect at 6 months in MSC group whereas the defect in the control group was increased. An intra-articular injection of autologous AD-MSCs provided satisfactory functional improvement and pain relief for patients with knee osteoarthritis in the outpatient setting, without causing adverse events at 6 months' follow-up. Larger sample size and long-term follow-up are required. Stem Cells Translational Medicine 2019;8:504-511.
| S-EPMC6525553 | biostudies-literature
Project description:PurposeThe management of knee pain secondary to meniscal tears with osteoarthritis is limited by the poor inherent healing potential of the meniscus. Previous studies have reported on the benefit of autologous micro-fragmented fat as a therapeutic for various knee pathologies. The goal of this prospective pilot study was to determine the safety and potential treatment effect of micro-fragmented adipose tissue injection for patients with knee pain secondary to osteoarthritis and meniscal tears who have failed conservative management.MethodsTwenty subjects with knee pain secondary to osteoarthritis with associated meniscal tear after failed conservative management were enrolled in the study. Numeric Pain Scale (NPS) and Knee Injury and Osteoarthritis Outcome Scale (KOOS) following ultrasound-guided intra-meniscal and intra-articular micro-fragmented adipose tissue injections were examined at three, six and 12 months.ResultsThe mean NPS revealed a significant decrease in patient pain at the 1-year time point compared with baseline (5.45 to 2.21, p < .001). Similarly, overall, mean KOOS symptoms significantly improved from 57.7 to 78.2 (p < .001), with all 4 KOOS subscales demonstrating significant improvement at the final one year follow-up. One subject developed uncomplicated cellulitis at the harvest site which was treated with oral antibiotics. Other complications were minor and mostly limited to adipose harvest.ConclusionThis study demonstrated that micro-fragmented adipose tissue injected directly into a torn meniscus and knee joint using ultrasound guidance represents a safe and potentially efficacious treatment option for patients with knee pain suffering from degenerative arthritis and degenerative meniscal tears. A larger, randomized, controlled trial is warranted to determine efficacy.Trial registrationClinicaltrials.org Identifier: NCT03714659.
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