Correlating the Osteoarthritic Knee Microenvironment to Clinical Outcome After Treatment With Regenexx®SD Treatment (KneeOA)

Single-center, lab blinded to include up to 400 subjects with knee osteoarthritis. Collection of synovial fluid from diseased knee before and after Regenexx®SD treatment will serve as the experimental condition, i.e. the osteoarthritic knee.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Biological: Regenexx SD® procedure

Detailed Description

Single-center, laboratory blinded to include up to 400 subjects with knee osteoarthritis in unilateral or bilateral knees treated with Regenexx® SD in the osteoarthritic knee/s.Initial study procedures include baseline evaluation of medical history, knee history, knee examination, medication use, MRI, and subject-reported outcomes.

Subjects will be enrolled within the 120 days prior to Regenexx® SD injection. A preoperative visit will occur at the time of enrollment. Collection of synovial fluid from the OA knee/s will serve as the experimental condition, i.e. the osteoarthritic knee.Each osteoarthritic subject will undergo withdrawal of knee joint synovial fluid for each knee being treated (0.3-0.5 ml) which will be analyzed by the research laboratory via multiplexed enzyme linked immunosorbent assay (ELISA) and dimethylmethylene blue assay (DMMB) at pre-injection (2-8 days before Regenexx® SD treatment) and post-injection (2-8 days after Regenexx® SD). Documentation of osteoarthritic joint characteristics and injection procedure details will be recorded throughout the study.

The unaffected knee joint will undergo no treatment, but bilateral knees may be treated.

Components of the synovial fluid will be correlated to post-treatment clinical outcomes, which include patient-reported questionnaires as well as assessment of post-injection complications, adverse events, re-injections and surgical interventions. Patient-reported clinical outcomes are comprised of the IKDC Subjective Knee Evaluation, the Lower Extremity Function Scale, Numeric Pain Scale and a Patient Reported Percent Improvement form.

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Voluntary signature of the IRB approved Informed Consent
2. Unilateral or bilateral osteoarthritic male or female ages 35-85
3. Pain, swelling, and/or functional disability in the affected knee consistent with osteoarthritis in the knee joint
4. Physical examination consistent with osteoarthritis in one knee joint
5. Kellgren-Lawrence grade 2 or greater knee osteoarthritis and/or diagnostic MRI imaging of the affected knee showing osteoarthritis (i.e. chondral loss, fissuring, defect, bone marrow lesion, meniscus tear, synovial thickening, etc…)
6. Is independent, ambulatory, and can comply with all post-operative evaluations and visits

Exclusion Criteria:

1. Knee injections of any type within 3 months prior to the study.
2. Knee surgery within 6 months prior to the study.
3. Inflammatory or auto-immune based joint diseases or other lower extremity pathology (e.g., rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, polymyalgia, polymyositis, gout pseudogout)
4. Quinolone or Statin induced myopathy/tendinopathy
5. Severe neurogenic inflammation of the cutaneous nerves about the knee or thigh
6. Contraindications for MRI
7. Condition represents a worker's compensation case
8. Currently involved in a health-related litigation procedure
9. Is pregnant
10. Bleeding disorders
11. Currently taking anticoagulant or immunosuppressive medication
12. Allergy or intolerance to study medication
13. Use of chronic opioid
14. Documented history of drug abuse within six months of treatment
15. Any other condition, that in the opinion of the investigator, that would preclude the patient from enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Regenexx-SD procedure; Measure components of knee synovial fluid collected 2-4 days before and after Regenexx SD procedure	Biological: Regenexx SD® procedure; Correlate patient outcomes 6 months after receiving the Regenexx SD procedure with measurements of synovial fluid collected before and after procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between components in knee synovial fluid to patient-reported outcomes post-procedure.	Synovial fluid components include cytokine, matrix metalloproteinase levels, and catabolic cartilage breakdown products. These components of synovial fluid will be correlated to the following patient-reported outcomes 6 months after procedure: the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation form.	6 months after Regenexx-SD procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of synovial fluid contents	Comparison of cytokine, matrix metalloproteinase concentration levels and cartilage breakdown product levels from pre-Regenexx SD treatment to post-Regenexx SD treatment.	fluid taken ~2-4 days before procedure and ~2-4 days after procedure

Collaborators and Investigators

• Sponsor: Regenexx, LLC
• Investigators: Study Director: Neven Steinmetz, Ph.D., Regenexx, LLC; Principal Investigator: Christopher J Centeno, M.D., Regenexx, LLC

Publications and helpful links

General Publications

• Bain BJ. Morbidity associated with bone marrow aspiration and trephine biopsy - a review of UK data for 2004. Haematologica. 2006 Sep;91(9):1293-4.
• Centeno CJ, Schultz JR, Cheever M, Freeman M, Faulkner S, Robinson B, Hanson R. Safety and complications reporting update on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique. Curr Stem Cell Res Ther. 2011 Dec;6(4):368-78. doi: 10.2174/157488811797904371.
• Centeno CJ, Schultz JR, Cheever M, Robinson B, Freeman M, Marasco W. Safety and complications reporting on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique. Curr Stem Cell Res Ther. 2010 Mar;5(1):81-93. doi: 10.2174/157488810790442796.
• Nejadnik H, Hui JH, Feng Choong EP, Tai BC, Lee EH. Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am J Sports Med. 2010 Jun;38(6):1110-6. doi: 10.1177/0363546509359067. Epub 2010 Apr 14.
• Wakitani S, Okabe T, Horibe S, Mitsuoka T, Saito M, Koyama T, Nawata M, Tensho K, Kato H, Uematsu K, Kuroda R, Kurosaka M, Yoshiya S, Hattori K, Ohgushi H. Safety of autologous bone marrow-derived mesenchymal stem cell transplantation for cartilage repair in 41 patients with 45 joints followed for up to 11 years and 5 months. J Tissue Eng Regen Med. 2011 Feb;5(2):146-50. doi: 10.1002/term.299.
• Irrgang JJ, Anderson AF, Boland AL, Harner CD, Neyret P, Richmond JC, Shelbourne KD; International Knee Documentation Committee. Responsiveness of the International Knee Documentation Committee Subjective Knee Form. Am J Sports Med. 2006 Oct;34(10):1567-73. doi: 10.1177/0363546506288855. Epub 2006 Jul 26.

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2015
• Primary Completion (Actual): June 30, 2020
• Study Completion (Actual): August 19, 2021

Study Registration Dates

• First Submitted: September 30, 2015
• First Submitted That Met QC Criteria: July 25, 2016
• First Posted (Estimate): July 28, 2016

Study Record Updates

• Last Update Posted (Actual): July 8, 2022
• Last Update Submitted That Met QC Criteria: July 6, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: RSI2015-LAB02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No