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OsteoarthritisPhase 3MILESNCT03818737

Multicenter Trial of Stem Cell Therapy for Osteoarthritis (MILES)

A Phase 3 study testing Bone Marrow Derived MSCs, Adipose-derived MSCs and Umbilical Cord Tissue (UCT) MSCs in people with Osteoarthritis, run by Emory University at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 40 to 70 years
Conditions the study is for
Osteoarthritis
What is being tested?
Bone Marrow Derived MSCs, Adipose-derived MSCs and Umbilical Cord Tissue (UCT) MSCs
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
475 participants
Where
5 sitesUnited States
Study dates
28 Mar 2019to 31 May 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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

Who cannot join

  • 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
Show all 25Show fewer
  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites
  • The Emory Clinic

    Atlanta, Georgia, 30322

  • Duke University

    Durham, North Carolina, 27710

  • Sanford Health

    Fargo, North Dakota, 58103

  • Andrews Institute

    Gulf Breeze, Florida, 32561

  • Sanford Health

    Sioux Falls, South Dakota, 57104

Other trials in United States

About this study

Official title: Randomized Multicenter Phase 3 Single-blind Trial Comparing the Efficacy of Corticosteroid Control to Mesenchymal Stem Cell 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 for the Treatment of Unilateral Knee Osteoarthritis (OA)

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.

Read the 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.

Conditions
Osteoarthritis
Being tested
Bone Marrow Derived MSCs, Adipose-derived MSCs, Umbilical Cord Tissue (UCT) MSCs, Corticosteroid injection
Keywords
mesenchymal stem cells, corticosteroids, bone marrow aspiration, adipose-derived stromal vascular fraction
Medical subject headings
Osteoarthritis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bone Marrow Derived MSCsBiological

    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 MSCsBiological

    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.

  • Umbilical Cord Tissue (UCT) MSCsBiological

    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.

  • Corticosteroid injectionDrug

    Also called Depo-Medrol, Methylprednisolone

    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.

Study groups in NCT03818737
Study groupRoleWhat they receive
Bone Marrow Derived MSCsExperimentalParticipants 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).
Receives: Biological: Bone Marrow Derived MSCs
Adipose-derived MSCsExperimentalParticipants 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).
Receives: Biological: Adipose-derived MSCs
Umbilical Cord Tissue (UCT) MSCsExperimentalParticipants randomized to this arm will receive an injection into the knee joint of cryopreserved doses of umbilical cord tissue MSCs.
Receives: Biological: Umbilical Cord Tissue (UCT) MSCs
Corticosteroid InjectionActive comparatorParticipants 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.
Receives: Drug: Corticosteroid injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

Secondary outcomes (4)
  1. Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) - Total 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 KOOS has 42 items across all subscales and response options are given on a 5-point Likert scale where 0 = no problems and 4 = extreme problems. The sum of subscale scores is transformed to a scale ranging from 0 to 100 with 0 indicating extreme symptoms and 100 indicating no symptoms. 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.

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

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

    The EQ-5D-3L survey measures the severity of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participants will be asked to answer questions regarding these measures and to indicate their current experience on a scale from 1 to 3 (1 being "no problem" and 3 being "most extreme problem"). A sixth item asks participants to rate their current heath from 0 (worst imaginable) to 100 (best imaginable). The answers to these questions are converted into an index value based on the country respondents live in. Health state index scores typically range from less than 0 to 1, where 0 is a health state equivalent to death and 1 is perfect health. Positive values for the change from baseline score indicate improved health.

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

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

    The PROMIS-29 assesses seven health domains: physical function, anxiety, depression, fatigue, sleep disturbance, pain interference, and ability to participate in social roles and activities. Each of the seven domains has four questions which are scored on a five-point Likert scale. The PROMIS-29 scales are scored using a T-score metric method available at the Assessment Center website (http://assessmentcenter.net). A score of 50 points represents the population average for each scale, and 10 points represent one standard deviation. Scores higher than 50 indicate more of the specific scale's construct, which may indicate a desirable or an undesirable outcome.

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

  4. Overall MRI Grade of Osteoarthritis

    An MRI grade of osteoarthritis was calculated by rating features viewed by MRI (such as cartilage loss) in terms of severity and extent. Total scores range from 0 to 69 with higher values indicating more severe osteoarthritis.

    Measured: Baseline, Month 6, Month 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jan 2019
  2. Study start28 Mar 2019
  3. Primary completion31 May 2022
  4. Study completion31 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
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 blind
Who is masked
Participant
Enrolment
475 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03818737
Sponsor's protocol ID
IRB00108046
Acronym
MILES
Status last verified
Jul 2023
First submitted
24 Jan 2019
Last updated
27 Jul 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Nelson BL, Jayaram P, Boden SD, Mautner K, Gottschalk MB, Myer GD, Drissi H, Diekfuss JA. SPOT: An Early Detection Tool for Predicting Pain Trajectories Following Intra-Articular Injections. J Orthop Res. 2026 Sep;44(9):e70270. doi: 10.1002/jor.70270.

    PubMed 42671292
  • 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.

    PubMed 41014273
  • 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.

    PubMed 37919438

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bone Marrow Derived MSCs, Adipose-derived MSCs and Umbilical Cord Tissue (UCT) MSCs in people with Osteoarthritis, run by Emory University at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Visual Analog Pain Scale (VAS-pain) Score (time frame: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03818737, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2023.

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