Implantation of Allogenic Mesenchymal Stem Cell From Umbilical Cord Blood for Osteoarthritis Management

Study Overview
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Brief Summary
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Prevalence of osteoarthritis increases every year, as a chronic and progressive disease. Osteoarthritis also gives many negative impacts in socio-economic life. Current management of osteoarthritis only aimed to relieve pain but not to resolve the degeneration of cartilage. Mesenchymal stem cell is one kind of adult stem cell that has potency in tissue engineering. Sources of mesenchymal stem cell are bone marrow, adipose tissue and umbilical cord. Researchers want to explore the potential of umbilical cord as the source of allogeneic MSC, because the gaining process of MSC is not invasive. Some countries have started some In vitro studies, Animal studies, and human research, but in Indonesia the study of mesenchymal stem cell implantation from umbilical cord in genu osteoarthritis management has not been reported. This study will be held into two years in Cipto Mangunkusumo Hospital and include 9 participants minimally. The researcher also compares the efficacy and safety of MSC implantation from umbilical cord applied to genu osteoarthritis with synovial artificial and recombinant human growth hormone therapy.

Detailed Description
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This study is experimental clinical, randomized control trial. This study estimated time would be 24 months, from May 2016 until May 2018. Samples are obtained consecutively from all source population that meet criteria. This study divide the samples into three groups, synovial artificial group, MSC and synovial artificial combination group; MSC, Synovial, and recombinant human growth hormone group. The number of samples in each group is three. Subject Criteria Inclusion Criteria for MSC Donor from Umbilical Cord: Umbilical cord are collected from elective caesarean section from a fullterm pregnancies without any complication and free from HIV, Hepatitis B, C, D virus, Cytomegalovirus, Rubella Virus, and free from fungal and bacterial contamination. Recipient inclusion criteria of osteoarthritis samples are patients aged 30-80 years old, based on genu X-ray examination and Kellgren-Lawrence grading is I, II, and III, or KL grade III with corrective osteotomy, minimal Visual Analog Scale = 2 (0-10), unresponsive with pharmacological therapy, and also sign up the informed consent. Recipient exclusion criteria are Osteoarthritis KL grade IV, and secondary osteoarthritis due to trauma, infection, rheumatoid arthritis, congenital diseases, and autoimmune diseases, hypersensitivity of hyaluronan product, cancer, pregnant women. Drop Out Criteria patients are ruled out from this study while the research are held or they undergo another treatment that are not related to this study. All drop out subjects could get another treatment. Informed consent all of subjects must be filled and signed up before ruled in this study. As soon as after delivery, umbilical cord is collected and processed in sterile specimen 0,9% NaCl at 4oC during 8 hours. The umbilical cord transported to the laboratory and cultured in GMP lab, at UPTTK Sel Punca Cipto Mangunkusumo Hospital. Cellular viability and proliferation are evaluated after cell characterization test by flowcytometer. Sterility test are done three times to ensure cellular sterility. Subjects are positioned in supine position, site of injection are determined by the operator. Injection from superolateral or superomedial in extension knee position, injection from anterolateral or anteromedial in flexion knee position. Aseptic and antiseptic in site of injection use povidone iodine 3 times, then swab by alcohol. Local anesthetic by lidocaine 1% is injected subcutaneously. Monitoring at the site of injection encompass allergic reaction, pain, and swelling. Patients are approached to be followed up every three months, in 1st ,3rd ,6th ,12th month, for clinical examination, VAS, IKDC and WOMAC Score. Cartigram MRI are evaluated every six month, in 6th and 12th month.

Official Title
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Potency of Allogenic Umbilical Cord Mesenchymal Stem Cells for Osteoarthritis Management

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: Hyaluronic Acid
* Biological: Umbilical Cord Mesenchymal Stem Cell
* Biological: Recombinant Human Somatropin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 30-80 years old Kellgren-Lawrence grade I, II, and III, or KL grade III with corrective osteotomy according to knee x-ray examination Minimal VAS: 2 Unresponsive with pharmacological therapy Signed the informed consent Exclusion Criteria: Osteoarthritis KL grade IV Secondary osteoarthritis due to trauma, infection, rheumatoid arthritis, congenital diseases, autoimmune diseases Hypersensitivity to hyaluronic acid Malignancies (Previously or currently diagnosed) Pregnancy

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control<br>Week 1: Intraarticular injection of 2 ml hyaluronic acid (Synvisc-One® Hylan G-F 20, Sanofi-Aventis) Week 2: Intraarticular injection of 2 ml hyaluronic acid (Synvisc-One® Hylan G-F 20, Sanofi-Aventis) Week 3: Intraarticular injection of 2 ml hyaluronic acid (Synvisc-One® Hylan G-F 20, Sanofi-Aventis) | Drug: Hyaluronic Acid<br> <br> * Other names: Hyaluronan;|
| Experimental: Intervention 1<br>Week 1: Intraarticular injection of 10x10^6 unit of umbilical cord mesenchymal stem cells in 2 ml conditioned medium, 2 ml hyaluronic acid (Synvisc-One® Hylan G-F 20, Sanofi-Aventis) Week 2: Intraarticular injection of 2 ml hyaluronic acid (Synvisc-One® Hylan G-F 20, Sanofi-Aventis), 8 IU recombinant human somatropin (Novell-Eutropin®, Novell Pharmaceutical Laboratories) Week 3: Intraarticular injection of 2 ml hyaluronic acid (Synvisc-One® Hylan G-F 20, Sanofi-Aventis), 8 IU recombinant human somatropin (Novell-Eutropin®, Novell Pharmaceutical Laboratories) | Drug: Hyaluronic Acid<br> <br> * Other names: Hyaluronan;Biological: Umbilical Cord Mesenchymal Stem Cell<br> <br> Biological: Recombinant Human Somatropin<br> <br> |
| Experimental: Intervention 2<br>Week 1: Intraarticular injection of 10x10^6 unit of umbilical cord mesenchymal stem cells in 2 ml conditioned medium, 2 ml hyaluronic acid (Synvisc-One® Hylan G-F 20, Sanofi-Aventis) Week 2: Intraarticular injection of 2 ml hyaluronic acid (Synvisc-One® Hylan G-F 20, Sanofi-Aventis) Week 3: Intraarticular injection of 2 ml hyaluronic acid (Synvisc-One® Hylan G-F 20, Sanofi-Aventis) | Drug: Hyaluronic Acid<br> <br> * Other names: Hyaluronan;Biological: Umbilical Cord Mesenchymal Stem Cell<br> <br> |
| Experimental: Intervention 3<br>Week 1: Intraarticular injection of 10x10^6 unit of umbilical cord mesenchymal stem cells in 2 ml conditioned medium, 2 ml hyaluronic acid (Synvisc-One® Hylan G-F 20, Sanofi-Aventis) Week 2: Intraarticular injection of 2 ml hyaluronic acid (Synvisc-One® Hylan G-F 20, Sanofi-Aventis), 8 IU recombinant human somatropin (Novell-Eutropin®, Novell Pharmaceutical Laboratories) Week 3: Intraarticular injection of 2 ml hyaluronic acid (Synvisc-One® Hylan G-F 20, Sanofi-Aventis), 8 IU recombinant human somatropin (Novell-Eutropin®, Novell Pharmaceutical Laboratories) | Drug: Hyaluronic Acid<br> <br> * Other names: Hyaluronan;Biological: Recombinant Human Somatropin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cartilage T2 map score | MRI examination of the knee with additional T2 mapping software CartiGram (GE Healthcare, USA). T2 map sequence are obtained from the medial and lateral aspect of both femoral and tibial cartilage. | 6 months | 
| IKDC score | Subjective assessment of knee function using the International Knee Documentation Committee Subjective Knee Evaluation form. Scale ranges from 1 to 100, higher value indicates higher function. | 3 months | 
| WOMAC score | Subjective assessment of knee function using the the Western Ontario and McMaster Universities Osteoarthritis Index. Scale ranges from 100% to 1%, lower value indicates higher function. | 3 months | 
| VAS score | VAS score is used to assess knee pain experienced by subjects. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, Mesenchymal Stem Cells, Umbilical Cord