Clinical trial NCT03898388: Correlating the OA Knee Microenvironment to Outcomes After Regenexx-SD Treatment: A Multi-Site Study
Official title: A Prospective Analysis Correlating the Osteoarthritic Knee Microenvironment to Clinical Outcome After Treatment With Regenexx® SD Treatment: A Multi-Site Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Knee Osteoarthritis
Lead sponsor: Regenexx, LLC
Sponsor class: INDUSTRY
First posted: 2019-04-02
Enrollment: 47
Sex: ALL
Minimum age (years): 35
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 1
Primary purpose: TREATMENT

Brief summary: Multi-center study to include up to 600 subjects with knee osteoarthritis in unilateral or bilateral knees treated with Regenexx® SD in the osteoarthritic knee/s. Synovial fluid drawn from patients' knee/s prior to receiving Regenexx-SD treatment will be correlated with their clinical outcomes after treatment.

Detailed description: Initial study procedures include baseline evaluation of medical history, knee history, knee examination, medication use, MRI, and subject-reported outcomes.

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). 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.

The objective of this study is to correlate the pre- Regenexx-SD treatment levels of pro-inflammatory cytokines, anti-inflammatory cytokines, matrix metalloproteinases, and catabolic articular cartilage breakdown products in the osteoarthritic knee synovial fluid microenvironment with 6 month post-treatment clinical outcomes. This data will be used to establish a predictive a priori testing "model" to determine if a patient is a good candidate for the Regenexx-SD treatment based on their initial osteoarthritic knee synovial fluid microenvironment phenotype. It may also be used to determine if the micro-environment can be altered to improve outcome before receiving Regenexx-SD.

Incidence of post-operative complications, adverse events, re-injections, and surgical intervention and change in pain score will be considered while determining these direct and indirect associations upon completion of the Regenexx-SD treatment.

Components of the synovial fluid will be correlated to post-treatment clinical outcomes, which include several self-reported questionnaires as well as assessment of post-injection complications, adverse events, re-injections and surgical interventions. Patient reported questionnaires include IKDC Subjective Knee Evaluation, Lower Extremity Function Scale, Pain Scales and a Modified Single Assessment Numeric Evaluation (SANE).

Eligibility criteria: 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:

* 7) Knee injections of any type within 3 months prior to the study. 8) Knee surgery within 6 months prior to the study.

  9) Patient undergoing lavage with treatment

  10) 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) 11) Quinolone or statin-induced myopathy/tendinopathy 12) Severe neurogenic inflammation of the cutaneous nerves about the knee or thigh 13) Contraindications for MRI 14) Condition represents a worker's compensation case 15) Currently involved in a health-related litigation procedure 16) Is pregnant 17) Bleeding disorders 18) Currently taking anticoagulant or immunosuppressive medication 19) Allergy or intolerance to study medication 20) Use of chronic opioid 21) Documented history of drug abuse within six months of treatment 22) Any other condition, that in the opinion of the investigator, that would preclude the patient from enrollment

Primary outcomes:
measure: Correlation between components in knee synovial fluid to patient-reported outcomes post-procedure.
timeFrame: 6 months after Regenexx-SD treatment
Secondary outcomes:
measure: Correlation between components of synovial fluid to 12 month IKDC outcomes
timeFrame: 12 months
measure: Correlation between components of synovial fluid and 6 month pain score
timeFrame: 6 months
measure: Correlation between components of synovial fluid and 6 month Lower Extremity Function Scale (LEFS).
timeFrame: 6 months
measure: Correlation between components of synovial fluid and 6 month modified Single Assessment Numeric Evaluation (SANE)
timeFrame: 6 months
measure: Correlation between components of synovial fluid and 12 month pain scores
timeFrame: 12 months
measure: Correlation between components of synovial fluid and 12 month LEFS
timeFrame: 12 months
measure: Correlation between components of synovial fluid and modified SANE
timeFrame: 12 months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Interventional Orthopedics of Atlanta
state: Georgia
city: Des Moines
country: United States
facility: Regenexx Des Moines
state: Iowa
city: Las Vegas
country: United States
facility: Regenexx Las Vegas
state: Nevada
Study officials:
affiliation: Regenexx, LLC
name: Christopher Centeno, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Centeno CJ, Al-Sayegh H, Bashir J, Goodyear S, Freeman MD. A dose response analysis of a specific bone marrow concentrate treatment protocol for knee osteoarthritis. BMC Musculoskelet Disord. 2015 Sep 18;16:258. doi: 10.1186/s12891-015-0714-z.
citation: Centeno C, Sheinkop M, Dodson E, Stemper I, Williams C, Hyzy M, Ichim T, Freeman M. A specific protocol of autologous bone marrow concentrate and platelet products versus exercise therapy for symptomatic knee osteoarthritis: a randomized controlled trial with 2 year follow-up. J Transl Med. 2018 Dec 13;16(1):355. doi: 10.1186/s12967-018-1736-8.
citation: Themistocleous GS, Chloros GD, Kyrantzoulis IM, Georgokostas IA, Themistocleous MS, Papagelopoulos PJ, Savvidou OD. Effectiveness of a single intra-articular bone marrow aspirate concentrate (BMAC) injection in patients with grade 3 and 4 knee osteoarthritis. Heliyon. 2018 Oct 18;4(10):e00871. doi: 10.1016/j.heliyon.2018.e00871. eCollection 2018 Oct.
citation: Centeno CJ, Al-Sayegh H, Freeman MD, Smith J, Murrell WD, Bubnov R. A multi-center analysis of adverse events among two thousand, three hundred and seventy two adult patients undergoing adult autologous stem cell therapy for orthopaedic conditions. Int Orthop. 2016 Aug;40(8):1755-1765. doi: 10.1007/s00264-016-3162-y. Epub 2016 Mar 30.