Nonunion FracturePhase 2NCT01429012
Treatment of Atrophic Nonunion Fractures by Autologous Mesenchymal Stem Cell Percutaneous Grafting
A Phase 2 study testing Mesenchymal Stem Cells and Culture medium without MSC. in people with Nonunion Fracture, run by University of Liege at 1 site in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Nonunion Fracture
- What is being tested?
- Mesenchymal Stem Cells and Culture medium without MSC.
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteBelgium
- Study dates
- Nov 2012to Nov 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treatment of Atrophic Nonunion Fractures by Autologous Mesenchymal Stem Cell Percutaneous Grafting. A Randomized, Double-blind, Controlled Study
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
- Being tested
- Mesenchymal Stem Cells, Culture medium without MSC.
- Keywords
- bone, nonunion fracture, atrophic nonunion fracture, callus, mesenchymal stem cells, cell therapy, autologous, indium, Pet-scan
- Medical subject headings
- Fractures, Ununited, Callosities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mesenchymal Stem CellsBiological
Also called MSC
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.Other
2 ml of culture medium.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Mesenchymal Stem Cells |
| Culture medium without MSC. | Placebo comparator | Culture medium used to resuspend the Mesenchymal Stem Cells. Receives: Other: Culture medium without MSC. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of Mesenchymal Stem Cells injection in nonunion fractures.
Follow-up for revealing any significant immediate or late adverse effects.
Measured: 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).
Measured: 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
Radiological evaluation of the callus by standard X-rays and computed tomography (CT).
Measured: 2, 3, 4, 8 and 10 months
Timing of development of a partial or complete callus in the 2 groups.
Time necessary for a partial or a complete callus formation. Radiological evaluation of the callus by standard X-rays and computed tomography (CT).
Measured: 12 months for one injection or 18 months when a second injection is needed
Patient evaluation of pain and global satisfaction.
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.
Measured: 12 months
Proportion of patients achieving different degrees of functional success.
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
Measured: 2, 3, 4, 6, 8, 10 and 12 months
Incidence of adverse events and severe adverse events in the 2 groups.
Adverse events and serious adverse events will be continuously monitored .
Measured: 12 months for one injection and 18 months when a second injection is performed
Evaluation of early homing of Mesenchymal Stem Cells.
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.
Measured: 24 hours
Value of [18F]-NaF PET scans for early prediction of the onset of the bone healing process.
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).
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2011 (estimated)
- Study startNov 2012 (estimated)
- Primary completionNov 2016 (estimated)
- Study completionNov 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nonunion FractureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Liege
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yves Beguin, University of Liege
- Investigators
- Jean Philippe Hauzeur, MD, PhD, Principal investigator, University of LiegeYves Beguin, Prof, MD, PhD, Study chair, University of Liege
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01429012
- Sponsor's protocol ID
- TJT1101
- Status last verified
- May 2021
- First submitted
- 1 Sep 2011
- Last updated
- 12 May 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Atrophic Nonunion Fractures by Autologous Mesenchymal Stem Cell Percutaneous Grafting. A Randomized, Double-blind, Controlled Study
- ClinicalTrials.gov ID
- NCT01429012
- Acronym / sponsor ID
- TJT1101
- Conditions
- Nonunion Fracture
- Keywords
- bone, nonunion fracture, atrophic nonunion fracture, callus, mesenchymal stem cells, cell therapy, autologous, indium
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of LiegeUniversity, hospital or other
- Study start
- Nov 2012 (estimated)
- Primary completion
- Nov 2016 (estimated)
- Study completion
- Nov 2016 (estimated)
- First posted
- 5 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mesenchymal Stem Cells | Experimental | Biological: Mesenchymal Stem Cells2 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. |
| Culture medium without MSC. | Placebo comparator | Other: Culture medium without MSC.Culture medium used to resuspend the Mesenchymal Stem Cells. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mesenchymal Stem CellsAlso: MSCMesenchymal 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. | Biological | Mesenchymal Stem Cells |
| Culture medium without MSC.2 ml of culture medium. | Other | Culture medium without MSC. |
Primary outcome
Safety of Mesenchymal Stem Cells injection in nonunion fractures.
Time frame: 12 months
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
Radiological evaluation of the callus by standard X-rays and computed tomography (CT).
7 secondary outcomes
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
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
Patient evaluation of pain and global satisfaction.
Time frame: 12 months
Proportion of patients achieving different degrees of functional success.
Time frame: 2, 3, 4, 6, 8, 10 and 12 months
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
Evaluation of early homing of Mesenchymal Stem Cells.
Time frame: 24 hours
Value of [18F]-NaF PET scans for early prediction of the onset of the bone healing process.
Time frame: 3 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean Philippe Hauzeur, MD, PhD principal investigator
University of Liege
Yves Beguin, Prof, MD, PhD study chair
University of Liege
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mesenchymal Stem Cells and Culture medium without MSC. in people with Nonunion Fracture, run by University of Liege at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 12 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of Mesenchymal Stem Cells injection in nonunion fractures. (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2021.