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

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

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.

Study Overview

• Status: Completed
• Conditions: Osteoporosis; Spinal Fractures
• Intervention / Treatment: Biological: Fucosylated MSC for Osteoporosis

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Hospital Clínico Virgen de la Arrixaca

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Red de Terapia Celular
• Collaborators: Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia; Hospital Universitario Virgen de la Arrixaca; Public Health Service, Murcia; Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca; Spanish National Health System; 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

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: January 30, 2015
• First Submitted That Met QC Criteria: September 30, 2015
• First Posted (Estimate): October 2, 2015

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 7, 2020
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Fractures, Bone; Wounds and Injuries; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Spinal Injuries; Back Injuries; Osteoporosis; Spinal Fractures
• Other Study ID Numbers: CSM/OP/2011; 2012-005814-20 (EudraCT Number)