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

Osteoarthritis, Knee Clinical Trial

Official title:

Potency of Allogenic Umbilical Cord Mesenchymal Stem Cells for Osteoarthritis Management

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03800810
• Other study ID #: ISMMSCOA
• Status: Recruiting
• Phase: Early Phase 1
• Start date: May 2015
• Est. completion date: May 2019

Study information

• Verified date: January 2019
• Source: Indonesia University
• Contact: Ismail H Dilogo, MD, PhD
• Phone: +622144539917
• Email: ismailorthofkui[@]yahoo.co.id
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 9
• Est. completion date: May 2019
• Est. primary completion date: May 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis, Knee

Intervention

Drug:
• Hyaluronic Acid

Biological:
• Umbilical Cord Mesenchymal Stem Cell

• Recombinant Human Somatropin

Locations

Country	Name	City	State
Indonesia	Universitas Indonesia	Jakarta Pusat	Jakarta

Sponsors (1)

Lead Sponsor	Collaborator
Indonesia University

Country where clinical trial is conducted

Indonesia, 

References & Publications (10)

Dart AJ, Little CB, Hughes CE, Chu O, Dowling BA, Hodgson DR, Rose RJ, Johnson KA. Recombinant equine growth hormone administration: effects on synovial fluid biomarkers and cartilage metabolism in horses. Equine Vet J. 2003 May;35(3):302-7. — View Citation

Higgins LD, Taylor MK, Park D, Ghodadra N, Marchant M, Pietrobon R, Cook C; International Knee Documentation Committee. Reliability and validity of the International Knee Documentation Committee (IKDC) Subjective Knee Form. Joint Bone Spine. 2007 Dec;74(6):594-9. Epub 2007 Aug 6. — View Citation

Kim SB, Kwon DR, Kwak H, Shin YB, Han HJ, Lee JH, Choi SH. Additive effects of intra-articular injection of growth hormone and hyaluronic acid in rabbit model of collagenase-induced osteoarthritis. J Korean Med Sci. 2010 May;25(5):776-80. doi: 10.3346/jkms.2010.25.5.776. Epub 2010 Apr 16. — View Citation

Raynauld JP, Torrance GW, Band PA, Goldsmith CH, Tugwell P, Walker V, Schultz M, Bellamy N; Canadian Knee OA Study Group. A prospective, randomized, pragmatic, health outcomes trial evaluating the incorporation of hylan G-F 20 into the treatment paradigm for patients with knee osteoarthritis (Part 1 of 2): clinical results. Osteoarthritis Cartilage. 2002 Jul;10(7):506-17. — View Citation

Singh A, Goel SC, Gupta KK, Kumar M, Arun GR, Patil H, Kumaraswamy V, Jha S. The role of stem cells in osteoarthritis: An experimental study in rabbits. Bone Joint Res. 2014 Feb 13;3(2):32-7. doi: 10.1302/2046-3758.32.2000187. Print 2014. — View Citation

Sinusas K. Osteoarthritis: diagnosis and treatment. Am Fam Physician. 2012 Jan 1;85(1):49-56. Review. Erratum in: Am Fam Physician. 2012 Nov 15;86(10):893. — View Citation

Solomon L, Warwic DJ, Nagayam S. Osteoarthritis. In : Apple's System if Orthopaedics and Fractures 8th Edition.oxford University Press. New York : 2001. P 77-90

Tsai SY, Huang YC, Chueh LL, Yeh LS, Lin CS. Intra-articular transplantation of porcine adipose-derived stem cells for the treatment of canine osteoarthritis: A pilot study. World J Transplant. 2014 Sep 24;4(3):196-205. doi: 10.5500/wjt.v4.i3.196. — View Citation

Vangsness CT Jr, Farr J 2nd, Boyd J, Dellaero DT, Mills CR, LeRoux-Williams M. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. J Bone Joint Surg Am. 2014 Jan 15;96(2):90-8. doi: 10.2106/JBJS.M.00058. — View Citation

White DK, Keysor JJ, Lavalley MP, Lewis CE, Torner JC, Nevitt MC, Felson DT. Clinically important improvement in function is common in people with or at high risk of knee OA: the MOST study. J Rheumatol. 2010 Jun;37(6):1244-51. doi: 10.3899/jrheum.090989. Epub 2010 Apr 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	VAS score	VAS score is used to assess knee pain experienced by subjects.	3 months

External Links

•   12. Luijkx V, Pai V. Kellgren and Lawrence system for the classification of the osteoarthritis of the knee
•   Anonimous. WOMAC index
•   Hamami, MB. Growth Hormone
•   Lozada, CJ. Et al. Osteoarthritis