Multicenter Trial of Stem Cell Therapy for Osteoarthritis (MILES)

NCT03818737 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: IRB00108046
• Study Type: interventional
• Target: 475
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Osteoarthritis

Keywords

mesenchymal stem cells; corticosteroids; bone marrow aspiration; adipose-derived stromal vascular fraction

Outcome Measures

Primary Outcomes (2)

• Change in Visual Analog Pain Scale (VAS-pain) Score

  Pain assessment was performed using the Visual Analog Pain Scale (VAS-pain). The VAS-pain is self-completed by the participant. The respondent is asked to place a line perpendicular to the VAS line at the point that represents their pain intensity. Using a ruler, the score is determined by measuring the distance in millimeters (mm) on the line between the "no pain" anchor and the participant's mark, providing a range of scores from 0-100. The recommended cut points for VAS are: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm). The change in VAS-pain score is the score from the each follow-up visit subtracted from the baseline score. A negative value means that pain has reduced from what it was at baseline.

  Baseline, 1 month, 3 months, 6 months, 9 months, 12 months

• Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Pain Subscale Score

  The KOOS questionnaire assesses the participant's opinion about their osteoarthritis and associated problems. It consists of 5 subscales: pain, symptoms, activities of daily living (ADL) function, sport and recreation function, and knee related quality of life (QoL). The pain subscale has 9 items and response options are given on a 5-point Likert scale where 0 = no problems and 4 = extreme problems. Scores are transformed to a scale ranging from 0 to 100 with 0 indicating extreme symptoms and 100 indicating no symptoms. The change in KOOS-pain subscale score is the score from each follow-up visit subtracted from the baseline score. A negative value means that pain has worsened from what it was at baseline, while a positive value means that pain has improved from baseline.

  Baseline, 1 month, 3 months, 6 months, 9 months, 12 months

Secondary Outcomes (4)

• Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Total Score

  Baseline, 1 month, 3 months, 6 months, 9 months, 12 months

• Change in EuroQuality of Life (EQ-5D-3L) Index Score

  Baseline, 1 month, 3 months, 6 months, 9 months, 12 months

• Patient-Reported Outcomes Measurement Information System (PROMIS-29) Score

  Baseline, 1 month, 3 months, 6 months, 9 months, 12 months

• Overall MRI Grade of Osteoarthritis

  Baseline, Month 6, Month 12

Study Arms (4)

Bone Marrow Derived MSCs

EXPERIMENTAL

Participants randomized to this arm will undergo bone marrow aspiration and then will be further randomized to receive a standard orthobiologic injection into the knee joint of autologous bone marrow concentrate (BMAC).

Biological: Bone Marrow Derived MSCs

Adipose-derived MSCs

EXPERIMENTAL

Participants randomized to this arm will undergo small volume lipoplasty, and then will be further randomized to receive an injection into the knee joint of adipose-derived stromal vascular fraction (SVF).

Biological: Adipose-derived MSCs

Umbilical Cord Tissue (UCT) MSCs

EXPERIMENTAL

Participants randomized to this arm will receive an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.

Biological: Umbilical Cord Tissue (UCT) MSCs

Corticosteroid Injection

ACTIVE COMPARATOR

Participants randomized to the bone marrow derived MSC, adipose-derived MSC, or umbilical cord tissue MSC study arms will be further randomized within the arm in a 3:1 ratio to receive either MSCs derived from the study arm of the initial randomization or a corticosteroid (CS) injection. Participants randomized to the control group will receive an injection of corticosteroid into the knee joint.

Drug: Corticosteroid injection

Interventions

Bone Marrow Derived MSCs BIOLOGICAL

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.

Bone Marrow Derived MSCs

Adipose-derived MSCs BIOLOGICAL

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.

Adipose-derived MSCs

Umbilical Cord Tissue (UCT) MSCs BIOLOGICAL

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.

Umbilical Cord Tissue (UCT) MSCs

Corticosteroid injection DRUG

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.

Also known as: Depo-Medrol, Methylprednisolone

Corticosteroid Injection

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• The Marcus Foundation: collaborator

Study Sites (5)

Andrews Institute

Gulf Breeze, Florida, 32561, United States

Location

The Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Sanford Health

Fargo, North Dakota, 58103, United States

Location

Sanford Health

Sioux Falls, South Dakota, 57104, United States

Location

Related Publications (2)

• Mautner K, Kaiser JM, Boggess B, Hackel J, Kurtenbach C, Noonan B, Shenvi N, Easley KA, Myer GD, Jayaram P, Gottschalk M, Boden S, Drissi H. Autologous Cell Injections for Knee Osteoarthritis Display Greater Responsiveness Than Allogenic Cellular Products and Corticosteroids in a Sex-Dependent Manner. Am J Sports Med. 2025 Oct;53(12):2889-2897. doi: 10.1177/03635465251365521. Epub 2025 Sep 27.

  PMID: 41014273 DERIVED

• Mautner K, Gottschalk M, Boden SD, Akard A, Bae WC, Black L, Boggess B, Chatterjee P, Chung CB, Easley KA, Gibson G, Hackel J, Jensen K, Kippner L, Kurtenbach C, Kurtzberg J, Mason RA, Noonan B, Roy K, Valentine V, Yeago C, Drissi H. Cell-based versus corticosteroid injections for knee pain in osteoarthritis: a randomized phase 3 trial. Nat Med. 2023 Dec;29(12):3120-3126. doi: 10.1038/s41591-023-02632-w. Epub 2023 Nov 2.

  PMID: 37919438 DERIVED

MeSH Terms

Conditions

Osteoarthritis

Interventions

Adrenal Cortex Hormones; Methylprednisolone Acetate; Methylprednisolone

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Kenneth Mautner, MD
• Organization: Emory University

kmautne@emory.edu

404-778-7142

Study Officials

• Hicham Drissi, PhD

  Emory University

  STUDY DIRECTOR

• Scott D Boden, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants will not know if they are receiving the MSC or corticosteroid injection.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: January 24, 2019
• First Posted: January 28, 2019
• Study Start: March 28, 2019
• Primary Completion: May 31, 2022
• Study Completion: May 31, 2022
• Last Updated: July 27, 2023
• Results First Posted: July 27, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)