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

U

University of Indonesia (UI)

Status and phase

Unknown
Early Phase 1

Conditions

Osteoarthritis, Knee

Treatments

Drug: Hyaluronic Acid
Biological: Recombinant Human Somatropin
Biological: Umbilical Cord Mesenchymal Stem Cell

Study type

Interventional

Funder types

Other

Identifiers

NCT03800810
ISMMSCOA

Details and patient eligibility

About

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.

Full description

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.

Enrollment

9 estimated patients

Sex

All

Ages

30 to 80 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Triple Blind

9 participants in 4 patient groups

Control
Experimental group
Description:
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)
Treatment:
Drug: Hyaluronic Acid
Intervention 1
Experimental group
Description:
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)
Treatment:
Biological: Umbilical Cord Mesenchymal Stem Cell
Biological: Recombinant Human Somatropin
Drug: Hyaluronic Acid
Intervention 2
Experimental group
Description:
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)
Treatment:
Biological: Umbilical Cord Mesenchymal Stem Cell
Drug: Hyaluronic Acid
Intervention 3
Experimental group
Description:
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)
Treatment:
Biological: Recombinant Human Somatropin
Drug: Hyaluronic Acid

Trial contacts and locations

1

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Central trial contact

Tri Kurniawati, BSc; Ismail H Dilogo, MD, PhD

Data sourced from clinicaltrials.gov

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