Evaluation of Mesenchymal Stem Cells to Treat Avascular Necrosis of the Hip (ORTHO-2)

Evaluation of Safety and Feasibility of Bone Marrow Derived Autologous MSCs to Enhance Bone Healing in Patients With Avascular Necrosis of the Femoral Head

The purpose is to assess the safety and feasibility of cellular therapy derived from bone marrow, to help bone healing in patients with avascular necrosis of the hip.

Study Overview

• Status: Completed
• Conditions: Avascular Necrosis of the Femoral Head
• Intervention / Treatment: Biological: Cultured autologous Mesenchymal Cells

Detailed Description

To assess the safety and feasibility of an in situ single injection of a high dose of autologous bone marrow-derived, in vitro expanded Mesenchymal stem cells, and its contribution to the resolution of the early stages of avascular osteonecrosis of the femoral head.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Créteil, France, 94000
    • Department of Orthopaedic Surgery, Hôpital Henri Mondor
  • Tours, France, 37044
    • Department of Orthopaedic Surgery, CHU Tours
• Germany
  • Tübingen, Germany, 72076
    • University Children's Hospital
  • Ulm, Germany, 8907581
    • Department of Orthopaedic Trauma, University of Ulm
• Italy
  • Bologna, Italy, 40136
    • Istituto Ortopedico Rizzoli
• Spain
  • Madrid, Spain, 28046
    • Servicio de Cirugía Ortopédica y Traumatología "A", Hospital La Paz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Age 18 to 65, both sexes

• Early avascular necrosis of the fem oral head (MRI diagnosis): Ficat and Arlet 0, 1, or 2 (Steinberg stages 0, I, IIA, IIB, or IIC)
• Sym ptom atic osteonecrosis with less than 6 months of evolution
• Able to provide informed consent, and signed informed consent
• Medical health care coverage

Exclusion Criteria:

• Pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control.
• Participation in another therapeutic trial in the previous 3 m onths
• Stages 3 or m ore (Ficat and Arlet) or III or m ore (Steinberg) of severe fem oral head osteonecrosis,primarily based on diagnosis by im aging (X-Rays, MRI).
• Flattening or collapse of the fem oral head (Steinberg stage IV) or articular cartilage collapse at the time of core decompression surgery.
• Septic arthritis.
• Stress fracture.
• Non-osteonecrosis metabolic bone diseases (particularly Paget's disease of bone, osteogenesis imperfecta, primary hyperparathyroidism , fibrous dysplasia monostotic, polyostotic McCune-Albright syndrome] and osteopetrosis).
• Any active bisphosphonate treatment or any history of intravenous (IV) treatment.
• History of prior or concurrent diagnosis of HIV-, Hepatitis-B- or Hepatitis-C-infection
• Active hepatitis B or hepatitis C infection at the time of screening.
• Known allergies to products involved in the production process of MSC.
• History of neoplasia or current neoplasia in any organ.
• Corticoid or immunosuppressive therapy more than one week in the two months prior to study inclusion
• Patients who will require continuous, systemic, high dose corticosteroid therapy (more than 7.5 m g/day) within 6 months after surgery.
• Patients who are in active treatment for cancer or blood dyscrasia, or have received chemotherapy, radiotherapy or immunotherapy in the past 2 years.
• History of regular alcohol consumption exceeding 2 drinks/day within 6 months of screening and/or history of illicit drug use.
• Serum AST (SGO T)/ALT (SGPT) > 2.5 X (institutional standard range).
• MRI-incompatible internal devices (pacemakers, aneurysm clips, etc).
• Body mass index (BMI) of 40 kg/m ² or greater.
• Patients unable to tolerate general anesthesia defined as an American Society of Anesthesiologists (ASA) criteria of > 2.
• Insulin dependent diabetes
• Patients with poorly controlled diabetes mellitus (HbA1C > 8%), or with peripheral neuropathy, or known concomitant vascular problems.
• Patients receiving treatment with hematopoietic growth factors or anti-vasculogenesis or antiangiogenesis treatment.
• Traumatic osteonecrosis.
• Adult in the care of a guardian (Subject legally protected)
• Im possibility to meet at the appointments for the clinical follow up.

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: Cultured autologous Mesenchymal Cells; Cultured Mesenchymal Cells from bone marrow isolation, expanded under GMP protocol in associated facilities and introduced at the end of the appropriate forage up to the femoral head under fluoroscopic control. 20x106 cells per cc in a single administration of 7cc	Biological: Cultured autologous Mesenchymal Cells; Cultured Mesenchymal Cells from bone marrow isolation, expanded under GMP protocol in associated facilities and introduced at the end of the appropriate forage up to the femoral head under fluoroscopic control.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complication rate	Includes early local complication rate plus global complication rate, as the percentage of patients with local or general complications at 52 weeks.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complication rate	Local and general complication rate	6,12,24,104 weeks
Progression of disease to the next stage		12 months
Amount of necrotic bone in the femoral head in MRI		12 weeks and 52 weeks
Pain (VAS)		6,12,24,52,104 weeks
serum levels of bone turnover markers		12 and 24 weeks

Collaborators and Investigators

• Sponsor: Universidad Autonoma de Madrid
• Investigators: Study Chair: Enrique Gomez-Barrena, Prof, Universidad Autonoma de Madrid, Hospital la Paz

Publications and helpful links

General Publications

• Gomez-Barrena E, Padilla-Eguiluz NG, Rosset P, Hernigou P, Baldini N, Ciapetti G, Gonzalo-Daganzo RM, Avendano-Sola C, Rouard H, Giordano R, Dominici M, Schrezenmeier H, Layrolle P, On Behalf Of The Reborne Consortium. Osteonecrosis of the Femoral Head Safely Healed with Autologous, Expanded, Bone Marrow-Derived Mesenchymal Stromal Cells in a Multicentric Trial with Minimum 5 Years Follow-Up. J Clin Med. 2021 Feb 1;10(3):508. doi: 10.3390/jcm10030508.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2014
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: February 12, 2014
• First Submitted That Met QC Criteria: February 14, 2014
• First Posted (Estimate): February 17, 2014

Study Record Updates

• Last Update Posted (Actual): October 14, 2021
• Last Update Submitted That Met QC Criteria: October 5, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: cell therapy; Mesenchymal stem cells; avascular necrosis of femoral head
• Additional Relevant MeSH Terms: Pathologic Processes; Musculoskeletal Diseases; Bone Diseases; Necrosis; Osteonecrosis; Femur Head Necrosis
• Other Study ID Numbers: ORTHO -2; 2012-002010-39 (EudraCT Number)