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

• ClinicalTrials.gov Identifier: NCT03800810
• Recruitment Status: Unknown
• First Posted: January 11, 2019
• Last Update Posted: January 23, 2019
• Sponsor: Indonesia University
• Information provided by (Responsible Party): Ismail Hadisoebroto Dilogo, Indonesia University

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Osteoarthritis, Knee	Drug: Hyaluronic Acid; Biological: Umbilical Cord Mesenchymal Stem Cell; Biological: Recombinant Human Somatropin	Early Phase 1

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Potency of Allogenic Umbilical Cord Mesenchymal Stem Cells for Osteoarthritis Management
• Study Start Date: May 2015
• Estimated Primary Completion Date: May 2019
• Estimated Study Completion Date: May 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Control; 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; Other Name: Hyaluronan
Experimental: Intervention 1; 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; Other Name: Hyaluronan; Biological: Umbilical Cord Mesenchymal Stem Cell; Biological: Recombinant Human Somatropin
Experimental: Intervention 2; 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; Other Name: Hyaluronan; Biological: Umbilical Cord Mesenchymal Stem Cell
Experimental: Intervention 3; 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; Other Name: Hyaluronan; Biological: Recombinant Human Somatropin

Outcome Measures

Primary Outcome Measures :

1. Cartilage T2 map score [ Time Frame: 6 months ]
   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.
2. IKDC score [ Time Frame: 3 months ]

   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. WOMAC score [ Time Frame: 3 months ]

   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.

4. VAS score [ Time Frame: 3 months ]
   VAS score is used to assess knee pain experienced by subjects.

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Ismail H Dilogo, MD, PhD; +622144539917; ismailorthofkui@yahoo.co.id

Contact: Tri Kurniawati, BSc; +622144539917; selpuncarscm@yahoo.co.id

Locations

Indonesia

Universitas Indonesia; Recruiting

Jakarta Pusat, Jakarta, Indonesia, 10430

Contact: Tri Kurniawati, BSc +622144539917 selpuncarscm@yahoo.co.id

Principal Investigator: Ismail H Dilogo, MD, PhD

Sponsors and Collaborators

Indonesia University

More Information

Additional Information:

Lozada, CJ. Et al. Osteoarthritis 

Hamami, MB. Growth Hormone 

12. Luijkx V, Pai V. Kellgren and Lawrence system for the classification of the osteoarthritis of the knee 

Anonimous. WOMAC index 

Publications:

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

• Responsible Party: Ismail Hadisoebroto Dilogo, Consultant, Department of Orthopaedics and Traumatology, Indonesia University
• ClinicalTrials.gov Identifier: NCT03800810
• Other Study ID Numbers: ISMMSCOA
• First Posted: January 11, 2019
• Last Update Posted: January 23, 2019
• Last Verified: January 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Name Gender Contact Address Sign up

Keywords provided by Ismail Hadisoebroto Dilogo, Indonesia University:

Osteoarthritis; Mesenchymal Stem Cells; Umbilical Cord

Additional relevant MeSH terms:

Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee; Arthritis; Hyaluronic Acid; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs; Viscosupplements; Protective Agents