Treatment of Atrophic Nonunion Fractures by Autologous Mesenchymal Stem Cell Percutaneous Grafting

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified January 2013 by University Hospital of Liege
Sponsor:
Information provided by (Responsible Party):
Yves Beguin, University Hospital of Liege
ClinicalTrials.gov Identifier:
NCT01429012
First received: September 1, 2011
Last updated: January 17, 2013
Last verified: January 2013
  Purpose

Bone fractures heal most of the time particularly well and without complications. The solidification takes rarely more than two to three months. The wound healing depends greatly on a good blood supply and needs several steps. These processes culminate in a new mass of heterogeneous tissue which is known as the fracture callus. Unfortunately, 2%-5% bone fractures cannot achieve a proper solidification and between the ununited fragments a scar tissue appears. This incorrect healing induces pain and even infections. When this situation persists more than 6 months, it is referred to as nonunion fracture, which will require some form of intervention to stimulate the natural healing process of the body. First of all, good surgical techniques with stable immobilization should be applied and local infection should be excluded. Then stimulation of the callus is required. Cell therapy with bone marrow cells has emerged as a promising new approach for bone regeneration. Animal studies as well as preliminary human studies have shown that Mesenchymal Stem Cells, a particular kind of stem cells isolated from the bone marrow, could induce callus formation when injected in the nonunion site of a broken bone.

In this study the investigators aim at determining whether Mesenchymal Stem Cells (MSC) isolated from the patient's bone marrow and injected in the nonunion site could be a safe and effective treatment for nonunion fractures. Patients will be randomized in two groups; one injected with Mesenchymal Stem Cell and the other injected with placebo. The investigators seek also to know how long it takes to develop the callus formation and whether there is a partial or a complete callus formation.


Condition Intervention Phase
Nonunion Fracture
Biological: Mesenchymal Stem Cells
Other: Culture medium without MSC.
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treatment of Atrophic Nonunion Fractures by Autologous Mesenchymal Stem Cell Percutaneous Grafting. A Randomized, Double-blind, Controlled Study

Resource links provided by NLM:


Further study details as provided by University Hospital of Liege:

Primary Outcome Measures:
  • Safety of Mesenchymal Stem Cells injection in nonunion fractures. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Follow-up for revealing any significant immediate or late adverse effects.

  • Proportion of patients receiving Mesenchymal Stem Cells that develop a partial or complete callus at 6 and 12 months, compared to patients receiving placebo. [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
    Radiological evaluation of the callus by standard X-rays and computed tomography (CT).


Secondary Outcome Measures:
  • Proportion of patients receiving Mensechymal Stem Cells that develop a partial or complete callus at 2, 3, 4, 8 and 10 months, compared to patients receiving placebo [ Time Frame: 2, 3, 4, 8 and 10 months ] [ Designated as safety issue: No ]
    Radiological evaluation of the callus by standard X-rays and computed tomography (CT).

  • Timing of development of a partial or complete callus in the 2 groups. [ Time Frame: 12 months for one injection or 18 months when a second injection is needed ] [ Designated as safety issue: No ]
    Time necessary for a partial or a complete callus formation. Radiological evaluation of the callus by standard X-rays and computed tomography (CT).

  • Patient evaluation of pain and global satisfaction. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    This evaluation will be measured through a 100-mm Visual Analogue Scale at 2, 3, 4, 6, 8, 10 and 12 months in the 2 groups.

  • Proportion of patients achieving different degrees of functional success. [ Time Frame: 2, 3, 4, 6, 8, 10 and 12 months ] [ Designated as safety issue: No ]

    The functional assessment will be evaluated in Mesenchymal Stem Cells treated and untreated patients by an orthopaedic surgeon and will include a 4-points scale:

    • 0 = only passive motion allowed
    • 1 = only active mobilization without any opposition allowed
    • 2 = active mobilization with some opposition and partial weight-bearing allowed
    • 3 = weight-bearing and full active mobilization allowed

  • Incidence of adverse events and severe adverse events in the 2 groups. [ Time Frame: 12 months for one injection and 18 months when a second injection is performed ] [ Designated as safety issue: Yes ]
    Adverse events and serious adverse events will be continuously monitored .

  • Evaluation of early homing of Mesenchymal Stem Cells. [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Indium radiolabeled Mesenchymal Stem Cells (MSC) will be visualized with a Siemens e-CAM dual head gamma camera: 10% of the total amount of MSC will be incubated with 200 µCi In-111-oxine. The radiolabelled cells will be mixed with the unlabelled ones. Twenty-four hours after injecting the cells into the target bone lesion, static images centered over the injection site and whole-body images will be acquired during 20 minutes. This will be performed with a Siemens e-CAM dual head gamma camera.

  • Value of [18F]-NaF PET scans for early prediction of the onset of the bone healing process. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    PET Fluor kinetics could identify early and perhaps quantify the increase of bone forming in the treated area. Four [18F]-NaF PET scan studies will be performed: at baseline, as well as around days 7-9 (1 week), 27-33 (one month) and 83-97 (three months).


Estimated Enrollment: 40
Study Start Date: October 2013
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mesenchymal Stem Cells

2 ml with 40 X 10E6 Mesenchymal Stem Cells (MSC) will be injected in the nonunion space of the bone fracture.

MSC will be injected even if the number of available cells is lower than 40 X 10E6.

The injection of MSC in the nonunion space will be performed percutaneously using a 3-mm trephine needle under fluoroscopic control and loco-regional or general anesthesia, as deemed appropriate by the anesthetist.

Biological: Mesenchymal Stem Cells
Mesenchymal Stem Cells. Dose= 40 X 10E6 in 2 ml. Frequency = one injection. If no evidence of a callus after 6 months a second injection can be proposed.
Other Name: MSC
Placebo Comparator: Culture medium without MSC.
Culture medium used to resuspend the Mesenchymal Stem Cells.
Other: Culture medium without MSC.
2 ml of culture medium.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female; female patients must use a reliable contraception method
  • Age ≥ 18 years
  • Fracture having no radiological callus after 6 months and absence of any hypertrophic bone reaction.
  • No sepsis
  • Good skin covering
  • Be able and willing to participate in the study
  • Written informed consent

Exclusion Criteria:

  • Evidence of malignancy (except non-melanoma skin cancer) in the past five years
  • Pregnancy or breastfeeding
  • Patient positive by serology or PCR for HIV, hepatitis B or C infection
  • Insufficient reduction of the fracture with displaced fragments
  • Evidence of local sepsis by clinical signs, biological parameters (CRP) and/or positive isotopic scan using Indium-labelled leucocytes
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01429012

Contacts
Contact: Yves Beguin, Prof, MD, PhD 32/04/3667201 yves.beguin@chu.ulg.ac.be
Contact: Jean-Philippe Hauzeur, MD 32/04/3667863 jean-philippe.hauzeur@chu.ulg.ac.be

Locations
Belgium
Liège University Hospital Not yet recruiting
Liège, Belgium, 4000
Contact: Yves Beguin, Prof; MD; PhD    32/4/3667201    yves.beguin@chu.ulg.ac.be   
Contact: Jean-Philippe Hauzer, MD; PhD    32/4/3667863    jean-philippe.hauzeur@chu.ulg.ac.be   
Sub-Investigator: Chantal Lechanteur, PhD         
Sub-Investigator: Etienne Baudoux, MD         
Sub-Investigator: Michel Malaise, Prof, MD, PhD         
Sub-Investigator: William Kurth, MD         
Sub-Investigator: Henri Van Cauwenberge, MD         
Sub-Investigator: Philippe Gillet, Prof, MD, PhD         
Sub-Investigator: Roland Hustinx, Prof, MD, PhD         
Sub-Investigator: Claire Bernard         
Sub-Investigator: Paolo Simoni, MD         
Sponsors and Collaborators
University Hospital of Liege
Investigators
Principal Investigator: Jean Philippe Hauzeur, MD, PhD University Hospital of Liege
Study Chair: Yves Beguin, Prof, MD, PhD University Hospital of Liege
  More Information

No publications provided

Responsible Party: Yves Beguin, MD, PhD, University Hospital of Liege
ClinicalTrials.gov Identifier: NCT01429012     History of Changes
Other Study ID Numbers: TJT1101
Study First Received: September 1, 2011
Last Updated: January 17, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by University Hospital of Liege:
bone
nonunion fracture
atrophic nonunion fracture
callus
mesenchymal stem cells
cell therapy
autologous
indium
Pet-scan

Additional relevant MeSH terms:
Fractures, Bone
Fractures, Ununited
Wounds and Injuries

ClinicalTrials.gov processed this record on October 23, 2014