Multicenter Trial of Stem Cell Therapy for Osteoarthritis (MILES)
Condition: Osteoarthritis
MeSH terms: Osteoarthritis
Study type: Interventional
Phase: Phase 3

Summary: 
      The study is a multicenter trial conducted to compare the effectiveness of an injection of a
      corticosteroid control to mesenchymal stem cell (MSC) preparations from autologous bone
      marrow concentrate (BMAC), adipose derived stem cells in the form of Stromal Vascular
      Fraction (SVF), and third-party human mesenchymal stem cells manufactured from umbilical cord
      tissue (UCT) for the treatment of unilateral Knee Osteoarthritis (OA). The study will be
      conducted in 4 sites in the United States, and a total of 480 participants will be enrolled
      in this study.
    

Detailed description: 
      Primary osteoarthritis is a debilitating disease characterized by extensive damage to the
      joints and excruciating pain leading to loss of activity and depression. Despite advances in
      diagnosis and relatively efficient control of nociception, to date, the quest for the
      development of a disease modifying osteoarthritis drug has proven unsuccessful. The potential
      of mesenchymal stem cells (MSCs) to inhibit inflammation while promoting healing makes them
      amenable for the treatment of various ailments ranging from cancer to genetic diseases. In
      orthopedic practice, autologous stem cell injections are performed to alleviate the pain
      associated with osteoarthritis. A serious gap in knowledge remains whether the currently used
      cellular treatments are beneficial in the long term and if one cell therapy outperforms
      another.

      The most popular form of autologous MSC therapy has been through the use of autologous bone
      marrow concentrate (BMAC). The rationale is that when a sample of bone marrow aspirate (BMA)
      is collected and the components that are not beneficial to the joint are filtered out (i.e.
      red blood cells, neutrophils, etc.) the remaining concentrate (MSCs, platelets, interleukins,
      etc) can have a "healing" effect on the environment in which it is injected. However it is
      still unknown as to how effective BMAC is for treating orthopedic conditions compared to
      other MSC procedures and the most important components of the BMAC mixture that could aid
      patients suffering from osteoarthritis.

      Adipose tissue has been found to have a large amount of MSCs versus that in bone marrow.
      These cells are currently being used in a variety of clinical research studies within the
      regenerative medicine field. Through a tissue process which includes washing and
      centrifuging, the cellular components can be extracted as a cell pellet, which is also known
      as stromal vascular fraction (SVF). Adipose derived SVF is obtained via liposuction, or the
      removal of adipose tissue via a suction method.

      Although the use of various stem cell preparations for knee osteoarthritis has become
      increasingly prevalent, well-designed studies with conclusive proof of comparative
      effectiveness and identification of the optimal cell source and "dose" have not been
      performed. This study is the first randomized study comparing three types of cellular
      treatments to corticosteroids. The main objective of the study is to identify a superior
      source of stem cells for the treatment of osteoarthritis and validate its advantages over
      corticosteroid injections as the traditional gold standard treatment.

      Participants will be randomized study arms with different types of MSCs (bone marrow derived
      MSC, adipose derived MSC, and umbilical cord tissue MSC) and then will be further randomized
      to receive an injection of the MSC type they were initially assigned to or corticosteroid.
      Participants randomized to bone marrow derived MSC or adipose derived MSC will undergo a
      procedure (bone marrow aspiration or liposuction). Participants will be blinded to whether
      they receive the MSC or corticosteroid injection.
    

Intervention name(s): Bone Marrow Derived MSCs; Adipose-derived MSCs; Umbilical Cord Tissue (UCT) MSCs; Corticosteroid injection
Intervention type(s): Biological; Biological; Biological; Drug
Intervention description(s): Autologous bone marrow concentrate (BMAC) is a standard orthobiologic injection for knee osteoarthritis. The procedure involves harvesting of bone marrow aspirate (BMA) from the posterior superior iliac spine (PSIS) and then following centrifugation in an FDA approved device (EmCyte GenesisCS Pure BMAC®-60 ml) will be injected back into the knee joint. All injections will be made via ultrasound guidance using a standard approach.; Adipose-derived Stromal Vascular Fraction (SVF) will be obtained from a mini lipoaspirate. The lipoaspirate will then be enzymatically digested to produce a SVF that will be injected into the knee joint. All injections will be made via ultrasound guidance using a standard approach.; Cryopreserved doses of umbilical cord tissue MSCs will be used. These MSCs were cryopreserved at P2 culture in plasmalyte A + 5% human serum albumin in 5 finger cryobags containing 20 million cells in 4 mL and stored under liquid nitrogen until shipment. Cells will be transported in a dry shipper and thawed at the study sites. The dose of MSCs will be aspirated from the cryobag into a sterile syringe and directly injected into the knee. All injections will be made via ultrasound guidance using a standard approach.; The corticosteroid injection is prepared by mixing 1cc of 40mg/dL depomedrol and 6cc of normal saline in a 10cc syringe will be made into the knee joint. All injections will be made via ultrasound guidance using a standard approach.
Other intervention name(s): Depo-Medrol; Methylprednisolone
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Acetate
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The study will include a parallel design using a blocked central randomization scheme of 1:1:1:1. Participants will first be randomized to have MSCs derived from either bone marrow, adipose tissue, or umbilical cord tissue. Then they will be further randomized to receive either an injection of MSCs (from bone marrow, adipose, or umbilical cord tissue, depending on the first randomization) or a corticosteroid injection.
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: mesenchymal stem cells; corticosteroids; bone marrow aspiration; adipose-derived stromal vascular fraction