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

NCT ID: NCT01429012

Last Updated: 2021-05-12

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2016-11-30

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.

Conditions

Nonunion Fracture

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Mesenchymal Stem Cells

Intervention Type: BIOLOGICAL

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.

Culture medium without MSC.

Culture medium used to resuspend the Mesenchymal Stem Cells.

Group Type: PLACEBO_COMPARATOR

Culture medium without MSC.

Intervention Type: OTHER

2 ml of culture medium.

Interventions

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.

Intervention Type: BIOLOGICAL

Culture medium without MSC.

2 ml of culture medium.

Intervention Type: OTHER

Other Intervention Names

MSC

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Liege

OTHER

Sponsor Role: lead

Responsible Party

Yves Beguin

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jean Philippe Hauzeur, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Liege

Yves Beguin, Prof, MD, PhD

Role: STUDY_CHAIR

University of Liege

Locations

Liège University Hospital

Liège, , Belgium

Countries

Belgium

Other Identifiers

TJT1101

Identifier Type: -

Identifier Source: org_study_id