Impact of Mesenchymal Stem Cells in Knee Osteoarthritis

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Yes
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 60 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

Knee Osteoarthritis Subjects. 1. Male or female 18-60 years of age. 2. Confirmed diagnosis of knee osteoarthritis based on clinical and radiographic findings. 3. Unilateral chronic knee pain >4 months. 4. Imaging findings consistent with mild-moderate generalized cartilage degeneration (MRI chondropathy or radiographic changes) 5. Failed non-invasive modalities of treatment. 6. Subjects must have the ability to understand and the willingness to sign a written informed consent document. 7. 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.

Inclusion Criteria:

1. Male or female 18-60 year of age. 2. Knee pain and/or effusion. 3. Inability to continue or difficulty in participation in recreational or professional sport. 4. MRI with Outerbridge Grade 4 focal chondral defect. 5. Subjects must have the ability to understand and the willingness to sign a written informed consent document. 6. 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.

Exclusion Criteria:

1. Radiographic findings consistent with Kellgren-Lawrence Stage 4 disease. 2. Focal chondral defect. 3. Major axial deviation (>5 degrees varus or valgus) 4. Concomitant ligamentous or meniscal injury. 5. BMI > 40 as defined by NIH Clinical Guidelines Body Mass Index. 6. Women who are pregnant, breastfeeding or unwilling to practice birth control during participation in the study. 7. 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. 8. Symptomatic active cardiac or respiratory disease that requires scheduled use of medication. 9. Neurologic disorder including, but not limited to epilepsy, Parkinson's disease, dementia, cerebrovascular disease, tumor of the nervous system, and amyotrophic lateral sclerosis. 10. 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. 11. Current immunosuppression from medication or disease. 12. History of systemic malignancy. 13. History of infection with hepatitis B, C, or HIV. 14. History of inflammatory arthropathy. 15. History of prior local knee infection. 16. Major surgeries, other than diagnostic surgery within 4 weeks. 17. 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. 18. Screening hematology with white blood cell count < 4.5 x 109 cells/L, hematocrit <30%, and platelets <150 x 109 platelets/L. 19. Have a known history of hypersensitivity or anaphylactic reaction to Dimethyl sulfoxide (DMSO) 20. Have been treated in the last 6 months before enrollment for alcohol and/or drug abuse in an inpatient substance abuse program. 21. Subject unlikely to complete the study as determined by the Investigator. 22. 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 Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03477942
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University Hospitals Cleveland Medical Center
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

James E Voos, MD
Principal Investigator Affiliation University Hospitals Cleveland Medical Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Musculoskeletal Pain, Knee Osteoarthritis, Cartilage Injury, Cartilage Degeneration
Arms & Interventions

Arms

Experimental: Osteoarthritis

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.

Experimental: Cartilage

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.

Interventions

Biological: - Autologous Mesenchymal Stem Cells

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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Cleveland, Ohio

Status

Recruiting

Address

University Hospital Cleveland Medical Center

Cleveland, Ohio, 44106

Site Contact

Jacob G Calcei, MD

[email protected]

216-286-7594