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

Osteoarthritis, Knee Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04351087
• Other study ID #: 2019H0448
• Status: Completed
• Phase: N/A
• Start date: March 3, 2020
• Est. completion date: July 5, 2022

Study information

• Verified date: June 2023
• Source: Ohio State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: July 5, 2022
• Est. primary completion date: July 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Microfragmented Adipose Tissue
• Osteoarthritis
• Osteoarthritis, Knee
• Platelet-Rich Plasma

Intervention

Device:
• 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.

Locations

Country	Name	City	State
United States	The Ohio State University Sports Medicine Center	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Ohio State University

Country where clinical trial is conducted

United States, 

References & Publications (14)

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. Erratum In: Am J Sports Med. 2017 Apr;45(5):NP10. — View Citation

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. — View Citation

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. — View Citation

De Francesco F, Ricci G, D'Andrea F, Nicoletti GF, Ferraro GA. Human Adipose Stem Cells: From Bench to Bedside. Tissue Eng Part B Rev. 2015 Dec;21(6):572-84. doi: 10.1089/ten.TEB.2014.0608. Epub 2015 Jun 17. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	KOOS Pain [Knee Injury and Osteoarthritis Outcome Score]	The Knee injury and Osteoarthritis Outcome Pain Score [KOOS questionnaire] is a self-reported outcome measure assessing the patient's opinion about the pain in their knee. Standardized answer options are given [5 Likert boxes] and each question is assigned a score from 0 to 4. A normalized score [100 indicating no pain and 0 indicating extreme pain] is calculated.	6 months
Secondary	VAS [Visual Analog Pain Scale] Pain Score	The visual analog pain scale [VAS] is a validated, subjective measure for acute and chronic pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between 0 [no pain] and 10 [worst pain].	Baseline, 1 month, 3 months, 6 months, and 12 months
Secondary	Tegner Activity Scale	The Tegner activity scale is a one-item score that graded activity based on work and sports activities on a scale of 0 to 10. Zero represents disability because of knee problems and 10 represents national or international level soccer.	Baseline, 1 month, 3 months, 6 months, and 12 months