Clinical trial NCT04453111: Efficacy of Bone-marrow-derived and Placenta-derived Multipotent Mesenchymal Stem / Stromal Cells for Osteoarthritis
Official title: Efficacy of Bone-marrow-derived and Placenta-derived Multipotent Mesenchymal Stem / Stromal Cells for Osteoarthritis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Knee Osteoarthritis
Keywords: BM-MMSCs;
P-MMSCs;
Hyaluronic Acid
Lead sponsor: Institute of Cell Therapy
Sponsor class: INDUSTRY
Collaborators: name: The Institute of Traumatology and Orthopedics of NAMS of Ukraine
name: Kyiv City Clinical Hospital № 6
First posted: 2020-07-01
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Experimental: HA + stem cells therapy Experimental Group 1: three intra-articular injection of allogeneic P-MMSCs with up to 2•107cells (target dose up to 6•107 cells) with 20 mg Hyaluronic Acid at 4-weeks intervals - 15 patients Experimental Group 2: three intra-articular injection of autologous BM-MMSCs up to 2•107cells (target dose up to 6•107 cells) with 20 mg Hyaluronic Acid at 4-weeks intervals - 15 patients Control Group: three intra-articular injection of 20 mg Hyaluronic Acid, no cell therapy - 15 patients
Primary purpose: TREATMENT

Brief summary: To define the clinical effects of intra-articular transplantation of bone-marrow-derived (BM-MMSCs) and placenta-derived multipotent mesenchymal stem / stromal cells (P-MMSCs) for knee osteoarthritis.

Detailed description: Multipotent mesenchymal stem / stromal cells (MMSCs) of different origin are the novel therapeutic agents that can slow down cartilage degeneration, improve reparation and ultimately prevent joint prosthetics. MSCs are capable to direct differentiation into chondrocytes, produce cytokines and growth factors with immunomodulatory and anti-inflammatory effects, stimulate angiogenesis, as well as induce chemotaxis of endogenous progenitors. Bone marrow-derived and placenta-derived MMSCs can be considered the most promising source for cell therapy of joints disorders according to availability, safety and expected therapeutic efficacy.

Eligibility criteria: Inclusion Criteria:

1. Clinical diagnosis of knee osteoarthritis.
2. Age: 18 to 75 years old.
3. Kellgren-Lawrence Grade 2 or 3 according to X-ray imaging.
4. Knee pain.
5. Written informed consent

Exclusion Criteria:

1. Age \<18 or \>75 years of age by time of infusion.
2. Participation in an on-going investigational therapeutic or device trial 30 days of consent.
3. Rheumatoid arthritis.
4. Psoriatic arthritis.
5. Juvenile idiopathic arthritis.
6. Gout.
7. Infectious arthritis.
8. Osteomyelitis.
9. Osteonecrosis.
10. Inflammatory arthritis.
11. Chondropathy.
12. Joint contracture.
13. Arthroplasty.
14. Arthroscopy within 6 months prior to study entry.
15. Intra-articular injection within 3 months prior to study entry.
16. Hormone intake.
17. Antiaggregants and anticoagulants intake.
18. Immunosuppressants intake.
19. Allergy to hyaluronic acid.
20. History of organ or cell transplantation.
21. Hematologic abnormality evidenced by hematocrit \< 25%, white blood cell \< 2,500/ul or platelet count \< 100,000/ul.
22. Active infection.
23. Positive for HIV antigen.
24. History of hepatitis B, hepatitis C.
25. History of malignancy in the last 5 years prior to study entry.
26. Active tumors.
27. History of myocardial infarction.
28. History of stroke.
29. Renal failure with chronic hemodialysis.
30. Liver Cirrhosis (ICGR 15 \>30%).
31. Chromosomal abnormality.
32. Peripheral nervous system disorders.
33. Cognitive or language barriers that prohibit obtaining informed consent or any study elements.
34. History of drug abuse or alcohol abuse, or documented medical, occupational, or legal problems arising from the use of alcohol or drugs within the past 24 months.
35. Pregnant/nursing women or women of child-bearing potential.
36. Other condition that limits lifespan to \< 1 year.

Primary outcomes:
measure: Number of participants with adverse events and changes in physical examinations, vital signs and the results of clinical lab tests.
timeFrame: 12 months
Secondary outcomes:
measure: Physical function improvement measured by Western Ontario and McMaster Universities Arthritis Index (WOMAC).
timeFrame: 12 months.
measure: Radiographic evidence. Whole-Organ Magnetic Resonance Imaging Score (WORMS)
timeFrame: 12 months
measure: Quality of Life (QOL) assessment
timeFrame: 12 months
measure: The Visual Analog Scale (VAS) assessment
timeFrame: 12 months
Other outcomes:
Locations:
city: Kyiv
country: Ukraine
facility: Institute of Cell Therapy
Study officials:
affiliation: Institute of Cell Therapy
name: Peter Nemtinov, MD
role: STUDY_DIRECTOR
References: