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Musculoskeletal PainPhase 1NCT03477942

Impact of Mesenchymal Stem Cells in Knee Osteoarthritis

A Phase 1 study testing Autologous Mesenchymal Stem Cells in people with Musculoskeletal Pain and Knee Osteoarthritis, run by University Hospitals Cleveland Medical Center at 1 site 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

Many patients with osteoarthritis of the knee fail non-operative measures and elect to have knee arthroplasty to improve their quality of life. If successful, intra-articular mesenchymal stem cell (MSC) injections into the knee may offer another viable non-operative treatment modality. Read more about this study

Who is it for?
Ages 18 to 60 yearsHealthy volunteers can take part
What is being tested?
Autologous Mesenchymal Stem Cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteUnited States
Study dates
1 Oct 2018to 31 Jul 2026
Phase
Phase 1
Are there results?
None posted in the registry

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 18 to 60 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Knee Osteoarthritis Subjects
  • Male or female 18-60 years of age
  • Confirmed diagnosis of knee osteoarthritis based on clinical and radiographic findings
  • Unilateral chronic knee pain >4 months
  • Imaging findings consistent with mild-moderate generalized cartilage degeneration (MRI chondropathy or radiographic changes)
  • Failed non-invasive modalities of treatment
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  • Subjects must have the ability to understand and the willingness to sign a written informed consent document
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of <1% per year during the treatment period. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (<12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptive that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Period abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception
  • Focal Chondral Defect Subjects
  • Male or female 18-60 year of age
  • Knee pain and/or effusion
  • Inability to continue or difficulty in participation in recreational or professional sport
  • MRI with Outerbridge Grade 4 focal chondral defect
  • Subjects must have the ability to understand and the willingness to sign a written informed consent document
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of <1% per year during the treatment period. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (<12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptive that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Period abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

Who cannot join

  • Radiographic findings consistent with Kellgren-Lawrence Stage 4 disease
  • Focal chondral defect
  • Major axial deviation (>5 degrees varus or valgus)
  • Concomitant ligamentous or meniscal injury
  • BMI > 40 as defined by NIH Clinical Guidelines Body Mass Index
  • Women who are pregnant, breastfeeding or unwilling to practice birth control during participation in the study
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  • Concurrent participation in another investigational trial involving systemic administration of agents (within the previous 30 days), or have received prior intra-articular injection of any form
  • Or plans to participate in any other allogeneic stem cell therapy trial during the 2-year follow-up period
  • Symptomatic active cardiac or respiratory disease that requires scheduled use of medication
  • Neurologic disorder including, but not limited to epilepsy, Parkinson's disease, dementia, cerebrovascular disease, tumor of the nervous system, and amyotrophic lateral sclerosis.
  • Psychiatric disorder including, but not limited to schizophrenia, bipolar disorder, personality disorder, depression, anxiety, or any other mental illness that would prevent the completion of the study
  • Current immunosuppression from medication or disease
  • History of systemic malignancy
  • History of infection with hepatitis B, C, or HIV
  • History of inflammatory arthropathy
  • History of prior local knee infection
  • Major surgeries, other than diagnostic surgery within 4 weeks
  • Contraindication to MRI:
  • Indwelling medical devices such as pacemakers, aneurysm clips, etc.
  • Indwelling metal from any other cause (trauma, etc.). To be excluded with history and/or radiographs, as necessary
  • Screening hematology with white blood cell count < 4.5 x 109 cells/L, hematocrit <30%, and platelets <150 x 109 platelets/L
  • Have a known history of hypersensitivity or anaphylactic reaction to Dimethyl sulfoxide (DMSO)
  • Have been treated in the last 6 months before enrollment for alcohol and/or drug abuse in an inpatient substance abuse program
  • Subject unlikely to complete the study as determined by the Investigator
  • Subjects must have normal marrow function, and be clinically stable with no significant changes in health status within 2 weeks prior to cell collection that the PI/Sub-Investigator deems relevant to exclude from participation. (See below for details of the cell collection procedure)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University Hospital Cleveland Medical Center

    Cleveland, Ohio, 44106

Other trials in United States

About this study

Official title: A Phase I Single Center Open Study to Assess the Safety and Efficacy of Intra-articular Mesenchymal Stem Cells in the Treatment of Knee Osteoarthritis and Chondral Defects of the Knee

Many patients with osteoarthritis of the knee fail non-operative measures and elect to have knee arthroplasty to improve their quality of life. If successful, intra-articular mesenchymal stem cell (MSC) injections into the knee may offer another viable non-operative treatment modality. Additionally, this modality may have reparative or regenerative potential, which could lead to the first treatment for osteoarthritis that treats the underlying disease as opposed to symptomatic control.

Additionally, there are no acceptable non-surgical treatments for focal chondral defects of the knee. Surgical treatments that do exist have diminished outcomes if performed on patients older than age 30-40 years. If successful, intra-articular MSC injections into the knee would represent the first non-operative treatment for focal chondral defects and also represent a potential option for treatment in patients over the age of 30-40 years.

This trial will be a prospective, single-center phase I pilot study to evaluate the safety and tolerability of a single intra-articular injection of autologous bone marrow-derived MSCs in 16 subjects, 8 who have knee osteoarthritis and 8 who have a focal chondral defect in the knee. Patients will undergo a bone marrow harvest procedure at the Dahms Clinical Research Unit (DCRU) of University Hospitals Cleveland Medical Center. MSCs will be isolated and expanded. After approximately 2-3 weeks, patients will return for an intra-articular injection of 50x106 MSCs Subsequent study visits will occur on post-injection day 7 and months 2, 6, 12, and 24. Safety of intra-articular injection of MSCs will be evaluated at study visits by interval history, physical examination and assessment of any adverse events that are observed/reported. Additionally, efficacy will be evaluated by having patients complete functional outcome measures including: Visual Analog Score (VAS) for pain, Knee Injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC) Subjective Knee Form, and Lysholm Knee Scale. These will be completed at the pre-treatment visit and then repeated at the 2, 6, 12, and 24-month follow-up visits. Lastly, T1 rho and T2 mapping on magnetic resonance imaging (MRI) will be used to assess for improved cartilage quality after intra-articular injection of MSCs. An MRI will be obtained at the pre-treatment visit. At the 12 and 24 month follow up visit, additional MRIs will be obtained and analyzed to compare the pre-treatment MRI to post-treatment MRIs.

Being tested
Autologous Mesenchymal Stem Cells
Medical subject headings
Musculoskeletal Pain, Osteoarthritis, Knee

What participants receive

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

  • Autologous Mesenchymal Stem CellsBiological

    Also called Stem Cell Injection

    Bone marrow will be harvested from each individual patient's iliac crest, followed by stem cell isolation, expansion and preparation. Stem cell will be injected approximately 3-4 weeks after bone marrow harvest, injecting 50x10^6 MSCs in the knee via a medial parapatellar approach under sterile technique in 8 patients with generalized knee OA or focal chondral defects.

Study groups in NCT03477942
Study groupRoleWhat they receive
OsteoarthritisExperimentalThe OA subgroup will be patients aged 18-60 years who have chronic knee pain due to early OA that have not responded to conservative, non-invasive measures such as physical therapy, medications, and activity modification.
Receives: Biological: Autologous Mesenchymal Stem Cells
CartilageExperimentalThe focal chondral defect subgroup will be patients aged 18-60 years who participate in recreational or professional sports and are symptomatic from a focal chondral defect shown on MRI.
Receives: Biological: Autologous Mesenchymal Stem Cells

What is being measured

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

  1. Primary Endpoint: Incidence of treatment emergent major adverse events directly related to MSC injection

    Establish the safety and tolerability of expended autologous intraarticular MSC injections into the knee by the incidence of no major adverse events (AE) determined to be directly related to MSC injection by the end of the 24 month follow up period. An AE is any untoward medical occurrence during the clinical investigation in a patient administered stem cells that does not have a causal relationship with the treatment that occurs from the time of consent through the last clinic visit at 24 months post-injection. An AE is therefore any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the administration of the investigational product, whether or not related to that investigational product. AEs will be described by duration (start and stop dates and times), severity, outcome, treatment and relation to investigational product, or if unrelated, the cause.

    Measured: 24 months

Secondary outcomes (3)

  1. Secondary Endpoint: Development of Pain following injection based on Visual Analog Scale scoring.

    Pain will be analyzed based on visual analog pain scores (VAS) by clinically and statistically significant amounts by six-month follow up and maintain these improvements throughout the two-year study period. Data analysis will be performed separately on the knee osteoarthritis subgroup and on the focal chondral defect subgroup. This will consist of a comparison of mean values for VAS scoring scales pre-operatively and at follow-up visits at 2, 6, 12, and 24-months. Clinically significant outcomes will be determined based on the minimal clinically important difference (MCID) occurring for each respective scale, which is defined as the smallest change score needed for the effect to be considered clinically relevant; described below. Specifically, VAS represents a patient-reported measurement tool used to quantify perceived level of pain, graded on a scale from 0 to 10 with 0 representing no pain and 10 representing the worse pain possible.

    Measured: 2, 6, 12 and 24 months

  2. Secondary Endpoint: Clinical Evaluation of Injection based on functional outcomes scoring using KOOS, IKDC and Lysholm scoring scales.

    Functional outcomes will be evaluated clinically and statistically throughout the study period. Data analysis will be performed on the knee osteoarthritis and the focal chondral defect subgroups. Mean values for Knee Injury and Osteoathritis Outcome Score (KOOS), International Knee Documentation Committee Score (IKDC), and Lysholm scoring scales pre-operatively and at follow-up visits at 2, 6, 12, and 24-months will be compared. KOOS is a qualitative assessment of knee pain, stiffness, function, and quality of life within the last week. The IKDC is a quantitative assessment of knee symptoms with daily and sporting activities with a high score of 100 representing no limitations or pain, with lower scores signifying pain or limitations in knee function. The Lysholm score rates knee pain and symptoms with a high score of 100, with scores > 90 representing excellent function and scores <65 representing poor function.

    Measured: 2, 6, 12 and 24 months

  3. Secondary Endpoint: Reparative potential of intra-articular MSCs based on improvement in cartilage quality using MRI.

    T1 rho and T2 mapping observed from MRIs at 1-year and 2-year follow-up to determine the reparative potential of intra-articular MSCs. T1 rho values increase as degenerative changes worsen; therefore, as cartilage quality improves, it is expected that T1 rho values would increase. T2 mapping values primarily reflect changes in water content and collagen anisotropy. Focal areas of increased T2 mapping values correlate with focal areas of cartilage damage; therefore, as cartilage quality improves, T2 mapping values would decrease. Clinically significant changes will be observed by comparing T1 rho and T2 values in areas of relatively preserved hyaline cartilage within our patients with the areas of degenerative change to utilize an internal control. Data analysis will consist of a comparison of mean values for quantitative T1 rho and T2 mapping data pre-operatively and at follow-up visits at 12 and 24-months.

    Measured: 12 and 24 months

Timeline

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

  1. First posted27 Mar 2018
  2. Study start1 Oct 2018
  3. Primary completion31 Jul 2026
  4. Study completion31 Jul 2026

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Prospective, single-center phase I pilot study to evaluate the safety and tolerability of a single intra-articular injection of autologous bone marrow-derived MSCs in 16 subjects, 8 who have knee osteoarthritis and 8 who have a focal chondral defect in the knee.
Masking
Single blind
Who is masked
Participant
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03477942
Sponsor's protocol ID
STUDY20180044
Status last verified
Oct 2026
First submitted
22 Feb 2018
Last updated
5 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: No patient protected health information will be shared outside the primary research team. All patient data will be de-identified.

Publications

  • Murphy L, Schwartz TA, Helmick CG, Renner JB, Tudor G, Koch G, Dragomir A, Kalsbeek WD, Luta G, Jordan JM. Lifetime risk of symptomatic knee osteoarthritis. Arthritis Rheum. 2008 Sep 15;59(9):1207-13. doi: 10.1002/art.24021.

    PubMed 18759314

  • Sato M, Uchida K, Nakajima H, Miyazaki T, Guerrero AR, Watanabe S, Roberts S, Baba H. Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis. Arthritis Res Ther. 2012 Feb 7;14(1):R31. doi: 10.1186/ar3735.

    PubMed 22314040

  • Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician. 2008 May-Jun;11(3):343-53.

    PubMed 18523506

  • Davatchi F, Abdollahi BS, Mohyeddin M, Shahram F, Nikbin B. Mesenchymal stem cell therapy for knee osteoarthritis. Preliminary report of four patients. Int J Rheum Dis. 2011 May;14(2):211-5. doi: 10.1111/j.1756-185X.2011.01599.x. Epub 2011 Mar 4.

    PubMed 21518322

  • Emadedin M, Aghdami N, Taghiyar L, Fazeli R, Moghadasali R, Jahangir S, Farjad R, Baghaban Eslaminejad M. Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis. Arch Iran Med. 2012 Jul;15(7):422-8.

    PubMed 22724879

  • Vega A, Martin-Ferrero MA, Del Canto F, Alberca M, Garcia V, Munar A, Orozco L, Soler R, Fuertes JJ, Huguet M, Sanchez A, Garcia-Sancho J. Treatment of Knee Osteoarthritis With Allogeneic Bone Marrow Mesenchymal Stem Cells: A Randomized Controlled Trial. Transplantation. 2015 Aug;99(8):1681-90. doi: 10.1097/TP.0000000000000678.

    PubMed 25822648

  • Koh YG, Jo SB, Kwon OR, Suh DS, Lee SW, Park SH, Choi YJ. Mesenchymal stem cell injections improve symptoms of knee osteoarthritis. Arthroscopy. 2013 Apr;29(4):748-55. doi: 10.1016/j.arthro.2012.11.017. Epub 2013 Jan 29.

    PubMed 23375182

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Autologous Mesenchymal Stem Cells in people with Musculoskeletal Pain and Knee Osteoarthritis, run by University Hospitals Cleveland Medical Center at 1 site 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 15 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 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Primary Endpoint: Incidence of treatment emergent major adverse events directly related to MSC injection (time frame: 24 months). 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 NCT03477942, which also lists 7 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 5 Oct 2026.

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