Impact of Mesenchymal Stem Cells in Knee Osteoarthritis

NCT03477942 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY20180044
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Musculoskeletal Pain; Knee Osteoarthritis; Cartilage Injury; Cartilage Degeneration

Outcome Measures

Primary Outcomes (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.

  24 months

Secondary Outcomes (3)

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

  2, 6, 12 and 24 months

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

  2, 6, 12 and 24 months

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

  12 and 24 months

Study Arms (2)

Osteoarthritis

EXPERIMENTAL

The 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.

Biological: Autologous Mesenchymal Stem Cells

Cartilage

EXPERIMENTAL

The 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.

Biological: Autologous Mesenchymal Stem Cells

Interventions

Autologous Mesenchymal Stem Cells BIOLOGICAL

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.

Also known as: Stem Cell Injection

Cartilage; Osteoarthritis

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University Hospitals Cleveland Medical Center: lead
• Case Western Reserve University: collaborator

Study Sites (1)

University Hospital Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Related Publications (7)

• 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.

  PMID: 18759314 BACKGROUND

• 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.

  PMID: 22314040 BACKGROUND

• 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.

  PMID: 18523506 BACKGROUND

• 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.

  PMID: 21518322 BACKGROUND

• 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.

  PMID: 22724879 BACKGROUND

• 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.

  PMID: 25822648 BACKGROUND

• 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.

  PMID: 23375182 BACKGROUND

MeSH Terms

Conditions

Musculoskeletal Pain; Osteoarthritis, Knee

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Osteoarthritis; Arthritis; Joint Diseases; Rheumatic Diseases

Study Officials

• James E Voos, MD

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chairman, Department of Orthopaedic Surgery

Model Details: 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.

Study Record Dates

• First Submitted: February 22, 2018
• First Posted: March 27, 2018
• Study Start: October 1, 2018
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: September 30, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)