Multicenter Trial of Stem Cell Therapy for Osteoarthritis (MILES)
Condition: Osteoarthritis
MeSH terms: Osteoarthritis
Intervention: Bone Marrow Derived MSCs; Adipose-derived MSCs; Umbilical Cord Tissue (UCT) MSCs; Corticosteroid injection
Intervention description: 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.
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Acetate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
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)
Masking description: Participants will not know if they are receiving the MSC or corticosteroid injection.
Enrollment: 475.0
Sex: All
Minimum age: 40 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: mesenchymal stem cells; corticosteroids; bone marrow aspiration; adipose-derived stromal vascular fraction

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age greater or equal to 40 but less than or equal to 70 years old

          -  Males and females

          -  Recent knee radiograph of the targeted knee (standing anteroposterior (AP) lateral and
             sunrise view)

          -  Diagnosis of OA in the targeted knee (radiographic evidence of OA in the medial and/or
             lateral tibiofemoral compartment, which would include one or more osteophytes on a
             standard radiograph taken within 3 months)

          -  Continued OA pain in the targeted knee despite conservative measures (per treating
             provider's discretion)

          -  Average daily Visual Analog Scale (VAS) ≥3

          -  Kellgren-Lawrence system of Grade II, III, or IV

          -  Subjects may have concomitant patellofemoral but they must have stage II or higher
             generalized knee OA

          -  Females of childbearing potential only, must have a negative pregnancy test done at
             screening prior to enrollment in the study

          -  Women and men of child-producing potential must agree to use acceptable contraception
             methods for the duration of the trial such as birth control pills or condoms with
             spermicide

        Exclusion Criteria:

          -  Clinically apparent tense effusion of the targeted knee

          -  Significant valgus/varus deformities (+/- 10 degrees)

          -  Viscosupplementation within 6 months in the targeted knee

          -  Other biologic injection (PRP or stem cell) within 1 year in the targeted knee

          -  Surgery in the targeted knee within the past 6 months (either open or scope)

          -  Systemic or intra-articular injection of corticosteroids in any joint within 3 months
             before screening

          -  Daily opioid use for the past three months

          -  History of malignancy in the previous 5 years prior to study entry, with the exception
             of in-situ cancers treated only by local excision with curative intent

          -  History of, or ongoing, autoimmune disorder that requires treatment with an
             immunosuppressive medication

          -  Active, suspected, or prior infection to the joint in the targeted knee

          -  Part of a vulnerable population per Office for Human Research Protections (OHRP)
             definition (pregnant women and breast-feeding women, cognitively impaired, prisoners,
             etc.)

          -  Unwilling to discontinue the use of Non-Steroidal Anti-Inflammatory (NSAID)s for 7
             calendar days prior to the procedure

          -  Unwilling to discontinue use of NSAIDS for 5 calendar days after procedure

          -  History of bleeding disorders or inflammatory joint disease

          -  Inability to hold anti-platelet therapy according to treating provider prior to
             procedure

          -  Subject is, in the opinion of the investigator, unable to comply with the requirements
             of the study protocol or is unsuitable for the study for any reason

          -  Uncontrolled diabetes

          -  Subject has an active workers' compensation case in progress with targeted knee

          -  Subject with insufficient amount of subcutaneous tissue

          -  Hemoglobin less than 10g/dL at the time of screening

          -  Leukocytes <3,000/μL; neutrophils <1,500/μL; lymphocytes <800/μL; platelets
             <100,000/μL at the time of screening

          -  Diagnosis of liver disease as defined by alanine aminotransferase (ALT) >3x the upper
             limit of age-determined normal (ULN) or total bilirubin > 1.5x ULN

          -  Subjects who have had greater than 3 corticosteroid injections in the targeted knee in
             the 12 months prior to screening or at the physician's discretion

          -  Subjects with a known diagnosis of osteoporosis

          -  Subjects with anticipated use of systemic corticosteroids during the study period for
             treatment of a chronic medical condition