Clinical Trial of Intravenous Infusion of Fucosylated Bone Marrow Mesenchyme Cells in Patients With Osteoporosis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of intravenous infusion of fucosylated autologous bone marrow cells as a new therapy in patients with established osteoporosis by a prospective, single-center, open, non-randomized and unblinded clinical trial.

Official Title
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Phase I Clinical Trial To Evaluate The Intravenous Infusion Of Autologous Fucosylated Bone Marrow Mesenchymal Cells Therapy In Patients With Established Osteoporosis and Low Impact Fractures

Conditions
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Osteoporosis, Spinal Fractures

Intervention / Treatment
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* Biological: Fucosylated MSC for Osteoporosis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with established osteoporosis according to standard clinical criteria. Patients who give their written informed consent to participate in the study consent. Meet all the inclusion criteria Exclusion Criteria: Patients with concomitant systemic disease in the opinion of the investigator. Patients with rheumatoid arthritis, ankylosing spondylitis, chronic polyarticular arthritis. Current patients with neoplasm or history of any malignancy in the last 10 years except basal carcinoma or epidermoid skin. Patients with genetic disorders that are associated with secondary osteoporosis: Hemochromatosis, hypophosphatasia, osteogenesis imperfecta, Ehlers-Danlos syndrome, Marfan syndrome, Riley Day, porphyria, storage diseases syndrome. Patients receiving immunosuppressive chemotherapy or that could interfere with the process of cell proliferation. Transplant patients: bone marrow, kidney, liver, heart, lung. Patients with clinical criteria and anesthetics that contraindicate well sedation or bone marrow extraction. Patients participating in a clinical trial in the last 6 months. Patients with positive serology for hepatitis B, hepatitis C or HIV. Patients with inability to understand informed consent. Patients who are pregnant or breast-feeding actively. Patients physically fertile, defined as all women physiologically capable of becoming pregnant, UNLESS they are using reliable methods of contraception.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fucosylated MSC for Osteoporosis<br>Autologous Bone Marrow fucosylated mesenchymal stem cells will be infused intravenously on Day 0. The first four patients enrolled will receive a single dose of 2 million cells/Kg and the last six patients enrolled, will receive a single dose of 5 million cells/kg. | Biological: Fucosylated MSC for Osteoporosis<br>* Aproximately 30 days before the infusion of the investigational product, patient bone marrow will be obtained according to standard practice of the Haematology University Hospital Virgen de la Arrixaca (HCUVA). Mononuclear bone marrow cells will be separated and cultured in GMP conditions to purify and obtain mesenchymal cell established dose range. The infusion day BM-MSCs will be fucosylated and resuspended in saline to a concentration of 5 million cells per 1 mL. Then, the final product will be packaged in syringes for intravenous administration to patients through a peripheral venous access.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of serious and non-serious adverse events related to the procedure. | During time frame the following items will be considered: Adverse effects related to the infusion moment. Occurrence of infectious complications after infusion of mesenchymal stem cells, because of the immunosuppressive effect of these cells. Appearance of procedure-related neoplasias. | 24 months from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of new fractures |  | 24 months from baseline | 
| Pain, measured by Visual Analog Scale | To measure pain, visual analogue scale (VAS) was used where 0 is no pain and 10 the worst pain imaginable. | 24 months from baseline | 
| Functionality, measured by Oswestry Disability Questionnaire | To identify the functional repercussion of lumbar pain, Oswestry Disability Questionnaire for back pain or Oswestry Disability Index is used. | 24 months from baseline | 
| Quality of Life, measured by EuroQoL-5D test | To measure the quality of life EuroQoL-5D psychometric test is used. | 24 months from baseline | 
| Bone resorption, measured by biochemical index | Aminoterminal telopeptide of type 1 collagen in the serum (serum NTX) (%) by ELISA technique. | 24 months from baseline | 
| Bone formation, measured by biochemical index | Osteocalcin in the serum by ELISA (BPG serum) (ng / mL) . | 24 months from baseline | 
| Bone formation, measured by biochemical index | Bone specific alkaline phosphatase in the serum by ELISA (serum FAO) (ug / L) | 24 months from baseline | 
| Bone formation, measured by biochemical index | Aminoterminal propeptide of procollagen type 1 in the serum by ELISA (serum P1NP) (ng / mL) | 24 months from baseline | 
| Bone metabolism, measured by biochemical index | Osteoprotegerin (OPG) (pmol / L) in the serum by ELISA. | 24 months from baseline | 
| Bone metabolism, measured by biochemical index | Ligand receptor activator of nuclear factor KB (RANKL) (pmol / L) in the serum by ELISA. | 24 months from baseline | 
| Bone Mineral Density , measured by dual energy x-ray absorptiometry (DXA) |  | 24 months from baseline | 
| Bone structure, measured by histomorphometric evaluation |  | baseline and 4 months from baseline | 
| Trabecular bone density measured by quantitative computed tomography of the radius |  | 24 months from baseline |