Clinical trial NCT01429012: Treatment of Atrophic Nonunion Fractures by Autologous Mesenchymal Stem Cell Percutaneous Grafting
Official title: Treatment of Atrophic Nonunion Fractures by Autologous Mesenchymal Stem Cell Percutaneous Grafting. A Randomized, Double-blind, Controlled Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Nonunion Fracture
Keywords: bone
nonunion fracture
atrophic nonunion fracture
callus
mesenchymal stem cells
cell therapy
autologous
indium
Pet-scan
Lead sponsor: University of Liege
Sponsor class: OTHER
First posted: 2011-09-05
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Safety of Mesenchymal Stem Cells injection in nonunion fractures.
timeFrame: 12 months
measure: Proportion of patients receiving Mesenchymal Stem Cells that develop a partial or complete callus at 6 and 12 months, compared to patients receiving placebo.
timeFrame: 6 and 12 months
Secondary outcomes:
measure: 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
timeFrame: 2, 3, 4, 8 and 10 months
measure: Timing of development of a partial or complete callus in the 2 groups.
timeFrame: 12 months for one injection or 18 months when a second injection is needed
measure: Patient evaluation of pain and global satisfaction.
timeFrame: 12 months
measure: Proportion of patients achieving different degrees of functional success.
timeFrame: 2, 3, 4, 6, 8, 10 and 12 months
measure: Incidence of adverse events and severe adverse events in the 2 groups.
timeFrame: 12 months for one injection and 18 months when a second injection is performed
measure: Evaluation of early homing of Mesenchymal Stem Cells.
timeFrame: 24 hours
measure: Value of [18F]-NaF PET scans for early prediction of the onset of the bone healing process.
timeFrame: 3 months
Other outcomes:
Locations:
city: Liège
country: Belgium
facility: Liège University Hospital
Study officials:
affiliation: University of Liege
name: Jean Philippe Hauzeur, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Liege
name: Yves Beguin, Prof, MD, PhD
role: STUDY_CHAIR
References: