Lipogems Prospective Study

Knee Osteoarthritis Clinical Trial

Official title:

Adipose Derived Stromal Cell Transplantation as an Adjunct to Arthroscopy in Treatment of Effusion Synovitis of the Early Degenerative Knee

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03922490
• Other study ID #: 2018-1534
• Status: Terminated
• Phase: Phase 4
• Start date: November 11, 2019
• Est. completion date: February 27, 2020

Study information

• Verified date: January 2023
• Source: Hospital for Special Surgery, New York
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to study the clinical outcomes and effects of the injection of fat-derived stem cells (the scientific name being "adipose derived autologous stem cell transplantation (ADAT)") as an addition to knee arthroscopy in the treatment of knee swelling and pain associated with mild to moderate knee osteoarthritis. Management of this condition remains a pervasive problem within orthopaedics. Lipogems is a Food and Drug Administration (FDA) approved technique. Lipogems is the name of the technology used to obtain stem cells from fat that will be aspirated/removed by suction from the abdomen. Fat will be processed to obtain stem cells which will then be injected into the knee after the physician completes knee arthroscopy. The study that we are asking patients to enroll in is important because it will attempt to answer the question about whether fat-derived stem cells added to knee arthroscopy is better, worse or no different than knee arthroscopy alone. Currently, without this study, we do not have an answer to this question.

Description:

Protocol Outline:

• The patient will undergo a diagnostic knee arthroscopy. This procedure would have been performed regardless of enrollment in the study. During the diagnostic knee arthroscopy, the surgeon will determine whether the patient is eligible to participate in the study.

• If the patient has a torn meniscus, inflamed joint lining or loose fragments in the knee, this will be removed and treated and he/she will still be eligible for the study.

• If, however, the physician determines that the patient needs more invasive treatments (such as cartilage transplantation, meniscal repair, removal of a substantial amount of your meniscus), then he/she will be excluded from the study and will not have fat tissue suctioned from his/her abdomen. The standard of care treatment will then proceed based on the physician's judgement.

• After the surgeon completes the arthroscopic procedure, the recommended amount of fat-derived stem cells (about 2 teaspoons) will be injected into the knee. There will be approximately 1 teaspoon of excess fat derived stem cells, which will be transported to our research facility so that the contents can be stored for later examination.

• After surgery, 5 visits are required by the patient over the following 12 months: at 2 weeks after surgery to monitor his/her incision, at 6 weeks, 12 weeks, 6 months and then finally 12 months.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: February 27, 2020
• Est. primary completion date: February 27, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Age between 18 and 70 years

• Knee pain and symptoms for >2 months - clicking, popping, giving way, pain with pivot or torque, pain that is episodic, and pain that is acute and localized to one joint

• Conservative treatment >4 weeks with one or more of:

• Non-steroidal Anti-inflammatory Drugs (NSAIDS) or acetaminophen or contraindication to use of NSAIDs and acetaminophen, Activity limitations, Physical Therapy (PT)

• Hospital for Special Surgery (HSS) MRI demonstrating grade 1-3 knee joint effusion/synovitis based on MRI Osteoarthritis Knee Score (MOAKS) criteria

• K-L grade 0-3 on radiographs and/or cartilage thinning on MRI w/ or w/o meniscal tear

• Ability to provide informed consent

Exclusion Criteria: The patients listed below are excluded due to potential confound factors which may alter clinical outcomes in either treatment group (1,3,4,5 7,8, 11, 12,13), if they may potentially cause a ceiling or floor effect to our clinical outcomes (2,6,) or if the treatment may constitute and undue risk to the patient or be outside of the standard of practice of treatment for that patient (1, 9, 10,14, 15, 16)

• 1. Under 18 years of age or skeletally immature

• 2. Grade 4 radiographic Osteoarthritis (OA) as defined by the K-L classification

• 3. Grade 4 chondral lesion of patellofemoral joint on diagnostic arthroscopy

• 4. Major coronal plane malalignment (>5° valgus or varus deviation)

• 5. Knee ligamentous instability

• 6. Pretreatment Numeric Rating Scale (NRS) pain score of <40 of 100

• 7. Systemic disorders such as diabetes, inflammatory arthritis (Rheumatoid Arthritis (RA), gout, psoriatic arthritis, Calcium Pyrophosphate Deposition Diseases (CPPD)), hematological diseases (coagulopathies),severe cardiovascular diseases, systemic infections, or immunodeficiencies.

• 8. History of septic arthritis

• 9. Ventral hernia (if abdominal donor site)

• 10. Lipomatous neoplasm in region of proposed donor site.

• 11. Current use of anticoagulant medications in the 5 days before surgical intervention

• 12. Recent intra-articular injection of corticosteroids (within 30 days) or

• 13. prior treatment with Hyaluronic acid (HA) in past 6 months.

• 14. Knee surgery within the previous 2 months

• 15. Pregnancy or possible pregnancy

• 16. Epilepsy

Related Conditions & MeSH terms

• Knee Osteoarthritis
• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Device:
• Lipogems Device PLUS debridement
Lipogems is the name of the technology used to obtain stem cells from the abdomen, which will then be injected into the knee after knee arthroscopy.

Procedure:
• Debridement only
Patients will undergo knee arthroscopy as a standard treatment for their condition but will not receive the fat-derived stem cell treatment nor will undergo any additional procedures.

Locations

Country	Name	City	State
United States	Hospital for Special Surgery	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Hospital for Special Surgery, New York

Country where clinical trial is conducted

United States, 

References & Publications (15)

Atukorala I, Kwoh CK, Guermazi A, Roemer F, Boudreau R, Hannon MJ, Hunter DJ. Response to: 'Synovitis in knee osteoarthritis: a precursor or concomitant feature?' by Zeng et al. Ann Rheum Dis. 2015 Oct;74(10):e59. doi: 10.1136/annrheumdis-2015-207800. Epub 2015 Aug 7. No abstract available. — View Citation

Ceserani V, Ferri A, Berenzi A, Benetti A, Ciusani E, Pascucci L, Bazzucchi C, Cocce V, Bonomi A, Pessina A, Ghezzi E, Zeira O, Ceccarelli P, Versari S, Tremolada C, Alessandri G. Angiogenic and anti-inflammatory properties of micro-fragmented fat tissue and its derived mesenchymal stromal cells. Vasc Cell. 2016 Aug 18;8:3. doi: 10.1186/s13221-016-0037-3. eCollection 2016. — View Citation

Fellows CR, Matta C, Zakany R, Khan IM, Mobasheri A. Adipose, Bone Marrow and Synovial Joint-Derived Mesenchymal Stem Cells for Cartilage Repair. Front Genet. 2016 Dec 20;7:213. doi: 10.3389/fgene.2016.00213. eCollection 2016. — View Citation

Jannelli E, Fontana A. Arthroscopic treatment of chondral defects in the hip: AMIC, MACI, microfragmented adipose tissue transplantation (MATT) and other options. SICOT J. 2017;3:43. doi: 10.1051/sicotj/2017029. Epub 2017 Jun 7. — View Citation

Karpinski K, Muller-Rath R, Niemeyer P, Angele P, Petersen W. Subgroups of patients with osteoarthritis and medial meniscus tear or crystal arthropathy benefit from arthroscopic treatment. Knee Surg Sports Traumatol Arthrosc. 2019 Mar;27(3):782-796. doi: 10.1007/s00167-018-5086-0. Epub 2018 Aug 20. — View Citation

Koh YG, Choi YJ, Kwon SK, Kim YS, Yeo JE. Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2015 May;23(5):1308-16. doi: 10.1007/s00167-013-2807-2. Epub 2013 Dec 11. — View Citation

Koh YG, Kwon OR, Kim YS, Choi YJ, Tak DH. Adipose-Derived Mesenchymal Stem Cells With Microfracture Versus Microfracture Alone: 2-Year Follow-up of a Prospective Randomized Trial. Arthroscopy. 2016 Jan;32(1):97-109. doi: 10.1016/j.arthro.2015.09.010. Epub 2015 Nov 14. — View Citation

MacFarlane LA, Yang H, Collins JE, Jarraya M, Guermazi A, Mandl LA, Martin SD, Wright J, Losina E, Katz JN; MeTeOR Investigator Group. Association of Changes in Effusion-Synovitis With Progression of Cartilage Damage Over Eighteen Months in Patients With Osteoarthritis and Meniscal Tear. Arthritis Rheumatol. 2019 Jan;71(1):73-81. doi: 10.1002/art.40660. Epub 2018 Nov 29. — View Citation

Marchal JA, Picon M, Peran M, Bueno C, Jimenez-Navarro M, Carrillo E, Boulaiz H, Rodriguez N, Alvarez P, Menendez P, de Teresa E, Aranega A. Purification and long-term expansion of multipotent endothelial-like cells with potential cardiovascular regeneration. Stem Cells Dev. 2012 Mar 1;21(4):562-74. doi: 10.1089/scd.2011.0072. Epub 2011 Jun 17. — View Citation

Randelli P, Menon A, Ragone V, Creo P, Bergante S, Randelli F, De Girolamo L, Alfieri Montrasio U, Banfi G, Cabitza P, Tettamanti G, Anastasia L. Lipogems Product Treatment Increases the Proliferation Rate of Human Tendon Stem Cells without Affecting Their Stemness and Differentiation Capability. Stem Cells Int. 2016;2016:4373410. doi: 10.1155/2016/4373410. Epub 2016 Jan 6. — View Citation

Schiavone Panni A, Vasso M, Braile A, Toro G, De Cicco A, Viggiano D, Lepore F. Preliminary results of autologous adipose-derived stem cells in early knee osteoarthritis: identification of a subpopulation with greater response. Int Orthop. 2019 Jan;43(1):7-13. doi: 10.1007/s00264-018-4182-6. Epub 2018 Oct 3. — View Citation

Striano R. D., Chen H., Bilbool N., Azatullah K., Hilado J., Horan K. Case Study: Non-Responsive Knee Pain with Osteoarthritis and Concurrent Meniscal Disease Treated With Autologous Micro-Fragmented Adipose Tissue Under Continuous Ultrasound Guidance CellR4 2015; 3 (5): e1690

Tremolada C, Ricordi C, Caplan AI, Ventura C. Mesenchymal Stem Cells in Lipogems, a Reverse Story: from Clinical Practice to Basic Science. Methods Mol Biol. 2016;1416:109-22. doi: 10.1007/978-1-4939-3584-0_6. — View Citation

Tremolada, Carlo. (2017). Mesenchymal Stem Cells and Regenerative Medicine: How Lipogems Technology Make Them Easy, Safe and More Effective to Use. MOJ Biology and Medicine. 2. 10.15406/mojbm.2017.02.00047.

Wang X, Jin X, Han W, Cao Y, Halliday A, Blizzard L, Pan F, Antony B, Cicuttini F, Jones G, Ding C. Cross-sectional and Longitudinal Associations between Knee Joint Effusion Synovitis and Knee Pain in Older Adults. J Rheumatol. 2016 Jan;43(1):121-30. doi: 10.3899/jrheum.150355. Epub 2015 Nov 15. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Knee Injury and Osteoarthritis Outcome (KOOS) Pain Subscale	Questions related to knee pain Scale range: 0-100 points (100 indicating no symptoms and 0 indicating extreme symptoms)	Baseline, 2-Week post-op, 6-Week post-op
Secondary	Change in Knee Injury and Osteoarthritis Outcome (KOOS) Symptoms	Questions related to other knee symptoms other than pain Scale range: 0-100 points (100 indicating no symptoms and 0 indicating extreme symptoms)	Baseline, 2-Week post-op, 6-Week post-op
Secondary	Change in Knee Injury and Osteoarthritis Outcome (KOOS) Function in Daily Living (ADL)	Questions related to function in daily living Scale range: 0-100 points (100 indicating no symptoms and 0 indicating extreme symptoms)	Baseline, 2-Week post-op, 6-Week post-op
Secondary	Change in Knee Injury and Osteoarthritis Outcome (KOOS) Function in Sport and Recreation (Sport/Rec)	Questions related to function in sport and recreation Scale range: 0-100 points (100 indicating no symptoms and 0 indicating extreme symptoms)	Baseline, 2-Week post-op, 6-Week post-op
Secondary	Change in Knee Injury and Osteoarthritis Outcome (KOOS) Quality of Life (QOL)	Questions related to knee-related quality of life Scale range: 0-100 points (100 indicating no symptoms and 0 indicating extreme symptoms)	Baseline, 2-Week post-op, 6-Week post-op
Secondary	Change in International Knee Documentation Committee (IKDC) Subjective Knee Form	Questions related to knee function over periods of time (100 indicating no symptoms and 0 indicating extreme symptoms)	Baseline, 2-Week post-op, 6-Week post-op
Secondary	Change in Numerical Pain Rating Scale (NPRS)	Numerical pain rating scale for pain in knee (0-10) (0: no pain - 10: worst pain imaginable)	Baseline, 2-Week post-op, 6-Week post-op
Secondary	Change in Marx Activity Rating Scale	Measures frequency of activity in healthiest and most active state during past year Includes four knee functions, each rated 0-4 total scale range 0-16 (higher score indicates more frequent participation/activity)	Baseline, 2-Week post-op, 6-Week post-op
Secondary	Change in Patient-Reported Outcomes Measurement Information System Global-10 Short Form (PROMIS-10)	10-item questionnaire with nine 5-point (as well as a single 11-point) rating scales. The results are used to calculate two summary scores: a Global Physical Health Score and a Global Mental Health score. These scores are then standardized to the general population, using the "T-Score". The average "T-Score" for the United States population is 50 points, with a standard deviation of 10 points. Higher scores indicate a healthier patient.; 11-point scale question recalculated to a 5 point scale. only 8 of 10 questions used for scoring calculations (Each sub-score is generated by 4/8 questions) - 4Qs, 5 points each Scale from 0-20 to calculate Global Mental Health Raw Score (higher score means better outcome) Scale from 0-20 to calculate Global Physical Health Raw Score (higher score means better outcome); The raw scores are then standardized to general population using the "T-score": Global physical health t-score range: 16.2-67.7 Global mental health t-score range: 21.2-67.6	Baseline, 2-Week post-op, 6-Week post-op