Microfragmented Adipose Tissue Versus Platelet-rich Plasma for Knee Osteoarthritis: a Randomized Comparative Trial

NCT ID: NCT04351087

Last Updated: 2024-08-09

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

79 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-03

Study Completion Date

2022-07-05

Brief Summary

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The study aims to conduct a randomized trial comparing the clinical outcomes of PRP (standard intervention) versus Microfragmented adipose tissue (investigational) for the treatment of knee osteoarthritis.

Hypothesis: Both interventions will result in significant improvement in patient-reported outcomes. We hypothesize that Microfragmented adipose tissue will provide superior outcomes.

Detailed Description

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Background

Knee osteoarthritis is a leading cause of disability worldwide. Standard of care treatments for knee OA include activity modification, weight loss, therapeutic exercise and injections like corticosteroids and viscosupplement. These commonly used non-operative treatments focus on symptom palliation, but are not disease modifying.

Orthobiologics have emerged as a promising treatment for knee OA. The most widely studied orthobiologic is platelet-rich plasma (PRP). PRP is a dense concentration of platelets derived from autologous whole blood and platelets are concentrated 2-5x compared to baseline. The platelets have demonstrated anti-inflammatory and chondroprotective properties.6 PRP has been shown superior to placebo and viscosupplement for knee OA in several clinical trials.

While PRP is the most widely studied and used orthobiologic, it contains only platelets. Therefore, a simple, office-based intervention able to collect additional reparative cells to treat knee OA would be ideal. Adipose (fat) is a known source of reparative cells like pericytes and it can be easily and safely aspirated in the clinic. The adipose tissue aspiration and processing is accomplished through a simple process. After local anesthesia to the site of adipose aspiration (lower abdomen or buttock), 30ml of adipose is aspirated through a cannula. That adipose is then processed in accordance with FDA guidelines including minimal manipulation to remove oils.. Using minimally manipulated Microfragmented adipose tissue has been shown safe for use as injection therapy for knee OA for 3 years.

Methods:

Patients / Outcome Measures / Sample size: Patients with unilateral symptomatic knee OA will be recruited from the sports medicine and orthopedics clinics, as well as advertising flyers within the clinic. All patients' first visit will include a medical evaluation and assess best treatment plan for that patient, regardless of candidacy for this study. This evaluation includes x-rays of their knees as a standard part of the evaluation. If they meet criteria and choose to enroll, they will be randomly assigned to either the PRP or Microfragmented adipose tissuetreatment group. Patients will complete follow up visits and surveys at defined time points through 12 months.

Conditions

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Osteoarthritis, Knee Microfragmented Adipose Tissue Platelet-Rich Plasma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Two-treatment parallel-design
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Platelet Rich Plasma

157cc of whole blood will be harvested via standard venipuncture from the antecubital fossa and mixed with 24cc ACD-A (manufacturer recommends 8cc ACD-A per 52cc of whole blood). 156ml of whole blood will be processed in the FDA Cleared Angel cPRP system at 2% hematocrit. 1ml of whole blood and the resultant PRP will be analyzed in the Sysmex XN-350 for complete analysis (platelet, leukocyte, red blood cell counts). The remaining PRP will be injected under sterile technique using ultrasound-guidance through a superolateral approach. For patient comfort, 2cc of 1% lidocaine can be administered using a 26-gauge needle (into soft tissues only). PRP will then be injected using a 25-guage needle. A maximum of 6ml of PRP will be injected. Injection site will be cleaned and bandaged and patient will be dismissed with post-injection precautions and 1 month follow-up scheduled.

Group Type ACTIVE_COMPARATOR

Platelet Rich Plasma

Intervention Type DEVICE

Platelet rich plasma: 157cc of whole blood will be collected, processed, and injected into the knee joint under sterile technique using ultrasound-guidance.

Microfragmented adipose tissue: Adipose will be aspirated from the subcutaneous tissue of the buttock or abdomen, processed, and injected into the knee joint under sterile technique using ultrasound-guidance.

Microfragmented adipose tissue

Adipose is aspirated from the subcutaneous tissue of the buttock or abdomen. Aspiration site is injected with 10ml 1% lidocaine with epinephrine. A small poke incision is made with an 11-blade scalpel. Then 120ml of Klein solution is injected into the adipose tissue. Solution sits for 15 minutes to allow for adequate anesthesia. Aspiration cannula is inserted and moved in a back and forth motion for 2 minutes to allow for adipose aspiration. 30ml fat will be aspirated. Aspiration site is cleaned and bandaged. The aspirated fat is processed using the Lipogems system. 30ml of adipose is transferred to the device, saline is run through the device to remove oils and then approximately 5-7ml of adipose tissue is removed and ready for injection. The Microfragmented adipose tissue are then injected in identical fashion to the PRP above.

Group Type ACTIVE_COMPARATOR

Platelet Rich Plasma

Intervention Type DEVICE

Platelet rich plasma: 157cc of whole blood will be collected, processed, and injected into the knee joint under sterile technique using ultrasound-guidance.

Microfragmented adipose tissue: Adipose will be aspirated from the subcutaneous tissue of the buttock or abdomen, processed, and injected into the knee joint under sterile technique using ultrasound-guidance.

Interventions

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Platelet Rich Plasma

Platelet rich plasma: 157cc of whole blood will be collected, processed, and injected into the knee joint under sterile technique using ultrasound-guidance.

Microfragmented adipose tissue: Adipose will be aspirated from the subcutaneous tissue of the buttock or abdomen, processed, and injected into the knee joint under sterile technique using ultrasound-guidance.

Intervention Type DEVICE

Other Intervention Names

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Microfragmented adipose tissue

Eligibility Criteria

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Inclusion Criteria

* Age 25-75 years
* BMI \< 40
* Diagnosis of knee OA (primary and post-traumatic)
* Radiographic evidence of OA of the target knee (Kellgren-Lawrence grades 1-4)
* Continued OA pain in the target knee despite at least 6 weeks of 1 of the following nonoperative treatments: activity modification, weight loss attempt, physical therapy, or NSAID / acetaminophen.
* Knee Osteoarthritis Outcomes Score (KOOS)-Pain subscale 20-65
* Working knowledge of English language (to be able to complete all outcome scores)
* Ability to attend all follow-up appointments

Exclusion Criteria

* Isolated patellofemoral OA
* 3+ effusion of the target knee (stroke test grading system)
* Significant (10 degree) valgus or varus deformities
* Prior injection therapy:
* Steroid injection in target knee in the last 3 months
* Viscosupplementation in target knee in the last 6 months
* PRP in the target knee in the last 1 year
* No other cellular treatments in index knee (bone marrow, amniotic suspensions etc) all time
* Participation in any experimental device or drug study within 1 year before screening visit
* Oral or IM steroids for last 3 months
* Medical condition that may impact outcomes of procedure including:
* anemia
* thrombocytopenia
* bleeding disorders
* inflammatory disorders like rheumatoid arthritis, lupus
* diabetes
* any history of cancer (other than non-melanoma skin malignancies)
* taking anticoagulants (aspirin, Plavix, eliquis, Xarelto, warfarin, lovenox)
* Taking immunosuppressants, having a severe systemic infection
* Previous cartilage repair procedure on the injured cartilage surface (ie, OATS, ACI, MFX)
* Previous surgery at the target knee within the past 1 year
* Any degree of cognitive impairment.
* OA of either hip
* Pregnancy, lactating, or intent to become pregnant during treatment period
* Gout
* History of infection or current infection at the affected joint
* Smoking
Minimum Eligible Age

25 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ohio State University

OTHER

Sponsor Role lead

Responsible Party

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Michael Baria

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Michael Baria, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

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The Ohio State University Sports Medicine Center

Columbus, Ohio, United States

Site Status

Countries

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United States

References

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Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, Bridgett L, Williams S, Guillemin F, Hill CL, Laslett LL, Jones G, Cicuttini F, Osborne R, Vos T, Buchbinder R, Woolf A, March L. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014 Jul;73(7):1323-30. doi: 10.1136/annrheumdis-2013-204763. Epub 2014 Feb 19.

Reference Type BACKGROUND
PMID: 24553908 (View on PubMed)

Hermann W, Lambova S, Muller-Ladner U. Current Treatment Options for Osteoarthritis. Curr Rheumatol Rev. 2018;14(2):108-116. doi: 10.2174/1573397113666170829155149.

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Liu Q, Niu J, Huang J, Ke Y, Tang X, Wu X, Li R, Li H, Zhi X, Wang K, Zhang Y, Lin J. Knee osteoarthritis and all-cause mortality: the Wuchuan Osteoarthritis Study. Osteoarthritis Cartilage. 2015 Jul;23(7):1154-7. doi: 10.1016/j.joca.2015.03.021. Epub 2015 Mar 25.

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Dai WL, Zhou AG, Zhang H, Zhang J. Efficacy of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Meta-analysis of Randomized Controlled Trials. Arthroscopy. 2017 Mar;33(3):659-670.e1. doi: 10.1016/j.arthro.2016.09.024. Epub 2016 Dec 22.

Reference Type BACKGROUND
PMID: 28012636 (View on PubMed)

Marx RE. Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent. 2001;10(4):225-8. doi: 10.1097/00008505-200110000-00002. No abstract available.

Reference Type BACKGROUND
PMID: 11813662 (View on PubMed)

Moussa M, Lajeunesse D, Hilal G, El Atat O, Haykal G, Serhal R, Chalhoub A, Khalil C, Alaaeddine N. Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage. Exp Cell Res. 2017 Mar 1;352(1):146-156. doi: 10.1016/j.yexcr.2017.02.012. Epub 2017 Feb 13.

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Cole BJ, Karas V, Hussey K, Pilz K, Fortier LA. Hyaluronic Acid Versus Platelet-Rich Plasma: A Prospective, Double-Blind Randomized Controlled Trial Comparing Clinical Outcomes and Effects on Intra-articular Biology for the Treatment of Knee Osteoarthritis. Am J Sports Med. 2017 Feb;45(2):339-346. doi: 10.1177/0363546516665809. Epub 2016 Oct 21.

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Gormeli G, Gormeli CA, Ataoglu B, Colak C, Aslanturk O, Ertem K. Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial. Knee Surg Sports Traumatol Arthrosc. 2017 Mar;25(3):958-965. doi: 10.1007/s00167-015-3705-6. Epub 2015 Aug 2.

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Sanchez M, Fiz N, Azofra J, Usabiaga J, Aduriz Recalde E, Garcia Gutierrez A, Albillos J, Garate R, Aguirre JJ, Padilla S, Orive G, Anitua E. A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis. Arthroscopy. 2012 Aug;28(8):1070-8. doi: 10.1016/j.arthro.2012.05.011.

Reference Type BACKGROUND
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Smith PA. Intra-articular Autologous Conditioned Plasma Injections Provide Safe and Efficacious Treatment for Knee Osteoarthritis: An FDA-Sanctioned, Randomized, Double-blind, Placebo-controlled Clinical Trial. Am J Sports Med. 2016 Apr;44(4):884-91. doi: 10.1177/0363546515624678. Epub 2016 Feb 1.

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Dragoo JL, Chang W. Arthroscopic Harvest of Adipose-Derived Mesenchymal Stem Cells From the Infrapatellar Fat Pad. Am J Sports Med. 2017 Nov;45(13):3119-3127. doi: 10.1177/0363546517719454. Epub 2017 Aug 17.

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Russo A, Condello V, Madonna V, Guerriero M, Zorzi C. Autologous and micro-fragmented adipose tissue for the treatment of diffuse degenerative knee osteoarthritis. J Exp Orthop. 2017 Oct 3;4(1):33. doi: 10.1186/s40634-017-0108-2.

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Russo A, Screpis D, Di Donato SL, Bonetti S, Piovan G, Zorzi C. Autologous micro-fragmented adipose tissue for the treatment of diffuse degenerative knee osteoarthritis: an update at 3 year follow-up. J Exp Orthop. 2018 Dec 19;5(1):52. doi: 10.1186/s40634-018-0169-x.

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Baria M, Barker T, Durgam S, Pedroza A, Flanigan D, Jia L, Kaeding C, Magnussen R. Microfragmented Adipose Tissue Is Equivalent to Platelet-Rich Plasma for Knee Osteoarthritis at 12 Months Posttreatment: A Randomized Controlled Trial. Orthop J Sports Med. 2024 Mar 18;12(3):23259671241233916. doi: 10.1177/23259671241233916. eCollection 2024 Mar.

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Baria M, Pedroza A, Kaeding C, Durgam S, Duerr R, Flanigan D, Borchers J, Magnussen R. Platelet-Rich Plasma Versus Microfragmented Adipose Tissue for Knee Osteoarthritis: A Randomized Controlled Trial. Orthop J Sports Med. 2022 Sep 16;10(9):23259671221120678. doi: 10.1177/23259671221120678. eCollection 2022 Sep.

Reference Type DERIVED
PMID: 36147791 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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2019H0448

Identifier Type: -

Identifier Source: org_study_id

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