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

NCT01429012 | Withdrawn Phase 2

• 1 other identifier: TJT1101
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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

Keywords

bone; nonunion fracture; atrophic nonunion fracture; callus; mesenchymal stem cells; cell therapy; autologous; indium; Pet-scan

Outcome Measures

Primary Outcomes (2)

• Safety of Mesenchymal Stem Cells injection in nonunion fractures.

  Follow-up for revealing any significant immediate or late adverse effects.

  12 months

• Proportion of patients receiving Mesenchymal Stem Cells that develop a partial or complete callus at 6 and 12 months, compared to patients receiving placebo.

  Radiological evaluation of the callus by standard X-rays and computed tomography (CT).

  6 and 12 months

Secondary Outcomes (7)

• 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

  2, 3, 4, 8 and 10 months

• Timing of development of a partial or complete callus in the 2 groups.

  12 months for one injection or 18 months when a second injection is needed

• Patient evaluation of pain and global satisfaction.

  12 months

• Proportion of patients achieving different degrees of functional success.

  2, 3, 4, 6, 8, 10 and 12 months

• Incidence of adverse events and severe adverse events in the 2 groups.

  12 months for one injection and 18 months when a second injection is performed

Study Arms (2)

Mesenchymal Stem Cells

EXPERIMENTAL

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

Culture medium without MSC.

PLACEBO COMPARATOR

Culture medium used to resuspend the Mesenchymal Stem Cells.

Other: Culture medium without MSC.

Interventions

Mesenchymal Stem Cells 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.

Also known as: MSC

Mesenchymal Stem Cells

Culture medium without MSC. OTHER

2 ml of culture medium.

Culture medium without MSC.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Liege: lead

Study Sites (1)

Liège University Hospital

Liège, 4000, Belgium

Location

MeSH Terms

Conditions

Fractures, Ununited; Callosities

Interventions

Culture Media

Condition Hierarchy (Ancestors)

Fractures, Bone; Wounds and Injuries; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Laboratory Chemicals; Specialty Uses of Chemicals; Chemical Actions and Uses; Equipment and Supplies

Study Officials

• Jean Philippe Hauzeur, MD, PhD

  University of Liege

  PRINCIPAL INVESTIGATOR

• Yves Beguin, Prof, MD, PhD

  University of Liege

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: September 1, 2011
• First Posted: September 5, 2011
• Study Start: November 1, 2012
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: May 12, 2021

Record last verified: 2021-05

Locations

BE (1)