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. 2021 Aug 20;16(1):514.
doi: 10.1186/s13018-021-02672-3.

Cell-free stem cell-derived extract formulation for treatment of knee osteoarthritis: study protocol for a preliminary non-randomized, open-label, multi-center feasibility and safety study

Ashim Gupta  1   2   3   4 , Nicola Maffulli  5   6   7   8 , Hugo C Rodriguez  9   10   11   12 , R Justin Mistovich  13   14 , Kristin Delfino  15 , Craig Cady  13   16 , Anne-Marie Fauser  16 , Echo D Cundiff  13 , Marte A Martinez  17 , Anish G Potty  13   10   7   18
Affiliations

Cell-free stem cell-derived extract formulation for treatment of knee osteoarthritis: study protocol for a preliminary non-randomized, open-label, multi-center feasibility and safety study

Ashim Gupta et al. J Orthop Surg Res. .

Abstract

Background: Musculoskeletal conditions are highly prevalent, and knee OA is most common. Current treatment modalities have limitations and either fail to solve the underlying pathophysiology or are highly invasive. To address these limitations, attention has focused on the use of biologics. The efficacy of these devices is attributed to presence of growth factors (GFs), cytokines (CKs), and extracellular vesicles (EVs). With this in mind, we formulated a novel cell-free stem cell-derived extract (CCM) from human progenitor endothelial stem cells (hPESCs). A preliminary study demonstrated the presence of essential components of regenerative medicine, namely GFs, CKs, and EVs, including exosomes, in CCM. The proposed study aims to evaluate the safety and efficacy of intraarticular injection of the novel cell-free stem cell-derived extract (CCM) for the treatment of knee OA.

Methods and analysis: This is a non-randomized, open-label, multi-center, prospective study in which the safety and efficacy of intraarticular CCM in patients suffering from grade II/III knee OA will be evaluated. Up to 20 patients with grade II/III OA who meet the inclusion and exclusion criteria will be consented and screened to recruit 12 patients to receive treatment. The study will be conducted at up to 2 sites within the USA, and the 12 participants will be followed for 24 months. The study participants will be monitored for adverse reactions and assessed using Numeric Pain Rating Scale (NPRS), Patient-Reported Outcomes Measurement Information System (PROMIS) Score, Knee Injury and Osteoarthritis Outcome Score Jr. (KOOS Jr.), 36-ietm short form survey (SF-36), Single Assessment Numeric Evaluation (SANE), physical exams, plain radiography, and magnetic resonance imaging (MRI) with Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score for improvements in pain, function, satisfaction, and cartilage regeneration.

Discussion: This prospective study will provide valuable information into the safety and efficacy of intraarticular administration of cell-free stem cell-derived extract (CCM) in patients suffering with grade II/III knee OA. The outcomes from this initial study of novel CCM will lay the foundation for a larger randomized, placebo-controlled, multi-center clinical trial of intraarticular CCM for symptomatic knee OA.

Trial registration: Registered on July 21, 2021. ClinicalTrials.gov NCT04971798.

Keywords: Clinical trial; Cytokines; Exosomes; Extracellular vesicles; Growth factors; Knee osteoarthritis; Musculoskeletal injuries; Progenitor cells; Regenerative medicine; Stem cells.

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Conflict of interest statement

AG, RJM, CC, EDC, and AGP owns equity in General Therapeutics. The remaining authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Summary of trial design
Fig. 2
Fig. 2
Standard protocol items: recommendations for interventional trials (SPIRIT) flowchart
See this image and copyright information in PMC

References

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