Clinical Trial of Intravenous Infusion of Fucosylated Bone Marrow Mesenchyme Cells in Patients With Osteoporosis (CSM/OP/2011)

• ClinicalTrials.gov Identifier: NCT02566655
• Recruitment Status: Completed
• First Posted: October 2, 2015
• Last Update Posted: October 8, 2020
• Sponsor: Red de Terapia Celular
• Collaborators: Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca; Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia; Hospital Universitario Virgen de la Arrixaca; Spanish National Health System; Public Health Service, Murcia; BIONAND, Universidad de Málaga, IBIMA, Ciber-bbn; Grupo de Tecnología Sanitaria CIBER-BBN, Inst. Biomecánica de Valencia
• Information provided by (Responsible Party): Red de Terapia Celular

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Osteoporosis; Spinal Fractures	Biological: Fucosylated MSC for Osteoporosis	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: September 2015
• Actual Primary Completion Date: December 2016
• Actual Study Completion Date: May 2018

Arms and Interventions

Arm

Intervention/treatment

Experimental: Fucosylated MSC for Osteoporosis; 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; 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.

Outcome Measures

Primary Outcome Measures :

1. Rate of serious and non-serious adverse events related to the procedure. [ Time Frame: 24 months from baseline ]

   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.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Spain

Hospital Clínico Virgen de la Arrixaca

El Palmar, Murcia, Spain, 30120

Sponsors and Collaborators

Red de Terapia Celular

Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca

Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia

Hospital Universitario Virgen de la Arrixaca

Spanish National Health System

Public Health Service, Murcia

BIONAND, Universidad de Málaga, IBIMA, Ciber-bbn

Grupo de Tecnología Sanitaria CIBER-BBN, Inst. Biomecánica de Valencia

Investigators

• Principal Investigator: Luis F Linares Ferrando, MD; Hospital Universitario Virgen de la Arrixaca

More Information

• Responsible Party: Red de Terapia Celular
• ClinicalTrials.gov Identifier: NCT02566655
• Other Study ID Numbers: CSM/OP/2011; 2012-005814-20 ( EudraCT Number )
• First Posted: October 2, 2015
• Last Update Posted: October 8, 2020
• Last Verified: November 2019

Additional relevant MeSH terms:

Osteoporosis; Spinal Fractures; Fractures, Bone; Wounds and Injuries; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Spinal Injuries; Back Injuries