Delayed Union After Fracture of Humerus, Tibial or FemurPhase 2OrthoCT1NCT01842477
Evaluation of Efficacy and Safety of Autologous MSCs Combined to Biomaterials to Enhance Bone Healing
A Phase 2 study testing Implantation of bone substitute plus autologous cultured mesenchymal cells in people with Delayed Union After Fracture of Humerus, Tibial or Femur, run by Institut National de la Santé Et de la Recherche Médicale, France at 5 sites in 4 countries.
Trial summary
Bone grafting is widely used in hospitals to repair injured, aged or diseased skeletal tissue. In Europe, about one million patients encounter a surgical bone reconstruction annually and the numbers are increasing due to our ageing population. Bone grafting intends to facilitate bone healing through osteogenesis (i.e. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Delayed Union After Fracture of Humerus, Tibial or Femur
- What is being tested?
- Implantation of bone substitute plus autologous cultured mesenchymal cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 5 sitesin 4 countries
- Study dates
- May 2013to 5 Feb 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to 65, both sexes
- Traumatic isolated closed or open Gustilo I and II humerus, tibial or femur diaphyseal or metaphyseal-diaphyseal fracture status delayed union or non-union
- At least 3 months from acute fracture
- Able to provide informed consent, and signed informed consent
- Patients (by themselves) should have medical health care coverage to be included in a research study
- Able to understand and accept the study constraints
Who cannot join
- Pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control
- Participation in another therapeutic trial in the previous 3 months
- Delayed union or non-union related to iatrogeny
- Segmental bone loss requiring specific therapy (bone transport, large structural allograft, megaprosthesis, etc)
- Vascular or neural injury
- Other fractures causing interference with weight bearing
Show all 18Show fewer
- Acute persistent chronic bacterial infections such as brucellosis, typhus, leprosy, relapsing fever, melioidosis and tularemia
- Visceral injuries of diseases interfering with callus formation (cranioencephalic trauma, etc.)
- History of bone harvesting on iliac crest contraindicating bone-marrow aspiration
- Corticoid or immunosuppressive therapy more than one week in the three months prior to study inclusion
- History of prior or concurrent diagnosis of HIV-, Syphilis, Hepatitis-B- or Hepatitis-C-infection (confirmed by serology or PCR)
- History of neoplasia or current neoplasia in any organ
- Subject legally protected, under legal guardianship, deprived of their liberty by judicial or administrative decision, subject of psychiatric care, or admission to a health facility.
- Impossibility to meet at the appointments for the follow up
- Insulin dependent diabetes
- Obesity (BMI > 30)
- Autoimmune inflammatory disease
- Current treatment by biphosphonate or stopped in the three months prior to study inclusion.
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
France2 sites
Depatment of Orthopaedic Surgery, Hôpital Henri Mondor
Créteil, 94000
Department of Orthopaedic Surgery, CHRU Tours
Tours, 37044
Spain1 site
Servicio de Cirugía Ortopédica y Traumatología "A", Hospital La Paz
Madrid, 28046
About this study
Official title: Evaluation of Efficacy and Safety of Autologous MSCs Combined to Biomaterials to Enhance Bone Healing in Patients With Delayed Consolidation After Long Bone Fracture Requiring Graft Apposition or Alternative Orthobiologics
Bone grafting is widely used in hospitals to repair injured, aged or diseased skeletal tissue. In Europe, about one million patients encounter a surgical bone reconstruction annually and the numbers are increasing due to our ageing population. Bone grafting intends to facilitate bone healing through osteogenesis (i.e. bone generation) at the site of damage, but this is only attained presently by including cells capable of forming bone into the augmentation.
Bone autograft is the safest and most effective grafting procedure, since it contains patient's own bone growing cells (to enhance osteogenesis) and proteins (to enhance osteoinduction), and it providing a scaffold for the new bone to grow into (osteoconduction). However, bone autograft is limited in quantity (about 20 cc) and its harvesting (e.g. from the iliac crest) represents an additional surgical intervention, with frequent consequent pain and complications.
We hypothesize that using autologous bone marrow cells expanded in GMP facility surgically implanted with synthetic bone substitutes contribute to the resolution of the health and socioeconomic complications of delayed union or non-union after diaphyseal and metaphyseal-diaphyseal fractures with safety and efficacy.
Read the detailed description
Tissue engineering combines bone marrow cells or mesenchymal stem cells (MSCs), synthetic scaffolds and molecular signals (growth or differentiating factors) in order to form hybrids constructs. For bone reconstruction purposes, human MSCs have been seeded and cultured on porous calcium phosphate ceramics in osteogenic media. Some clinical studies with low numbers of patients have been reported using this approach but the outcomes were inconsistent with low efficacy in bone regeneration. The reasons of the limited clinical success may be due to several bottlenecks in the multidisciplinary field of bone tissue engineering. The association in vitro of biomaterials and osteoprogenitor cells raises technical challenges and regulatory and ethic issues for the implementation of clinical trials, whereas the expansion of MSCs is now possible in GMP Facility.
The expected results are to obtain bone consolidation thus healing of delayed union or non-union, as proven by imaging techniques, without using bone graft. This will prove the efficacy of the proposed IMP based on pluripotent MSCs expanded in a GMP facility and mixed with granulated biphasic calcium phosphate in the surgical setting before implantation. No expected complications related to the procedure are expected. Changes in serum levels of bone turnover markers will be described.
- Being tested
- Implantation of bone substitute plus autologous cultured mesenchymal cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Implantation of bone substitute plus autologous cultured mesenchymal cellsBiological
Implantation surgery of a synthetic bone substitute associated with autologous bone marrow cells expanded
| Study group | Role | What they receive |
|---|---|---|
| Implantation surgery | Experimental | All the patients will have the implantation surgery. This trial is a one-arm study. Receives: Biological: Implantation of bone substitute plus autologous cultured mesenchymal cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complication rate as percentage of patients with local complications regarding the non-union treatment in the follow-up
Measured: At 6 weeks, 12 weeks, 24 weeks and 52 weeks after the implantation surgery
Secondary outcomes (5)
Number of patients with proven bone healing
Measured: 6 weeks, 12 weeks, and 24 weeks after the implantation surgery
Amount of radiological callus
Measured: 6 weeks, 12 weeks, and 24 weeks after the implantation surgery
Clinical consolidation
Measured: 6 weeks, 12 weeks, and 24 weeks after implantation surgery
No reoperation done or scheduled
Measured: 24 weeks after implantation surgery
Changes in serum levels of bone turnover markers
Measured: 6 weeks, 12 weeks, and 24 weeks after the implantation surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2013 (estimated)
- Study startMay 2013
- Primary completion5 Feb 2016
- Study completion5 Feb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Delayed Union After Fracture of Humerus, Tibial or FemurStudies of the same condition, open and under way.
- More trials run by Institut National de la Santé Et de la Recherche Médicale, FranceThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Sponsor type
- Other government
- Collaborators
- European Commission
- Responsible party
- Sponsor
- Investigators
- Enrique Gomez Barrena, Principal investigator, Universidad Autonoma de Madrid
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01842477
- Sponsor's protocol ID
- C11-12
- Other IDs
- 2011-005441-13
- Acronym
- OrthoCT1
- Status last verified
- Nov 2017
- First submitted
- 19 Apr 2013
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gomez-Barrena E, Rosset P, Gebhard F, Hernigou P, Baldini N, Rouard H, Sensebe L, Gonzalo-Daganzo RM, Giordano R, Padilla-Eguiluz N, Garcia-Rey E, Cordero-Ampuero J, Rubio-Suarez JC, Stanovici J, Ehrnthaller C, Huber-Lang M, Flouzat-Lachaniette CH, Chevallier N, Donati DM, Ciapetti G, Fleury S, Fernandez MN, Cabrera JR, Avendano-Sola C, Montemurro T, Panaitescu C, Veronesi E, Rojewski MT, Lotfi R, Dominici M, Schrezenmeier H, Layrolle P. Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial. Biomaterials. 2019 Mar;196:100-108. doi: 10.1016/j.biomaterials.2018.03.033. Epub 2018 Mar 19.
PubMed 29598897Granchi D, Gomez-Barrena E, Rojewski M, Rosset P, Layrolle P, Spazzoli B, Donati DM, Ciapetti G. Changes of Bone Turnover Markers in Long Bone Nonunions Treated with a Regenerative Approach. Stem Cells Int. 2017;2017:3674045. doi: 10.1155/2017/3674045. Epub 2017 Jun 20.
PubMed 28744314
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Efficacy and Safety of Autologous MSCs Combined to Biomaterials to Enhance Bone Healing in Patients With Delayed Consolidation After Long Bone Fracture Requiring Graft Apposition or Alternative Orthobiologics
- ClinicalTrials.gov ID
- NCT01842477
- Acronym / sponsor ID
- OrthoCT1 / C11-12
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Institut National de la Santé Et de la Recherche Médicale, FranceOther government
- Collaborators
- European Commission
- Study start
- May 2013
- Primary completion
- 5 Feb 2016 (actual)
- Study completion
- 5 Feb 2016 (actual)
- First posted
- 29 Apr 2013 (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 grafting is widely used in hospitals to repair injured, aged or diseased skeletal tissue. In Europe, about one million patients encounter a surgical bone reconstruction annually and the numbers are increasing due to our ageing population. Bone grafting intends to facilitate bone healing through osteogenesis (i.e. bone generation) at the site of damage, but this is only attained presently by including cells capable of forming bone into the augmentation.
Bone autograft is the safest and most effective grafting procedure, since it contains patient's own bone growing cells (to enhance osteogenesis) and proteins (to enhance osteoinduction), and it providing a scaffold for the new bone to grow into (osteoconduction). However, bone autograft is limited in quantity (about 20 cc) and its harvesting (e.g. from the iliac crest) represents an additional surgical intervention, with frequent consequent pain and complications.
We hypothesize that using autologous bone marrow cells expanded in GMP facility surgically implanted with synthetic bone substitutes contribute to the resolution of the health and socioeconomic complications of delayed union or non-union after diaphyseal and metaphyseal-diaphyseal fractures with safety and efficacy.
Detailed description
Tissue engineering combines bone marrow cells or mesenchymal stem cells (MSCs), synthetic scaffolds and molecular signals (growth or differentiating factors) in order to form hybrids constructs. For bone reconstruction purposes, human MSCs have been seeded and cultured on porous calcium phosphate ceramics in osteogenic media. Some clinical studies with low numbers of patients have been reported using this approach but the outcomes were inconsistent with low efficacy in bone regeneration. The reasons of the limited clinical success may be due to several bottlenecks in the multidisciplinary field of bone tissue engineering. The association in vitro of biomaterials and osteoprogenitor cells raises technical challenges and regulatory and ethic issues for the implementation of clinical trials, whereas the expansion of MSCs is now possible in GMP Facility.
The expected results are to obtain bone consolidation thus healing of delayed union or non-union, as proven by imaging techniques, without using bone graft. This will prove the efficacy of the proposed IMP based on pluripotent MSCs expanded in a GMP facility and mixed with granulated biphasic calcium phosphate in the surgical setting before implantation. No expected complications related to the procedure are expected. Changes in serum levels of bone turnover markers will be described.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Implantation surgery | Experimental | Biological: Implantation of bone substitute plus autologous cultured mesenchymal cellsAll the patients will have the implantation surgery. This trial is a one-arm study. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 18 to 65, both sexes
- Traumatic isolated closed or open Gustilo I and II humerus, tibial or femur diaphyseal or metaphyseal-diaphyseal fracture status delayed union or non-union
- At least 3 months from acute fracture
- Able to provide informed consent, and signed informed consent
- Patients (by themselves) should have medical health care coverage to be included in a research study
Key exclusion criteria (18 listed)
- Pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control
- Participation in another therapeutic trial in the previous 3 months
- Delayed union or non-union related to iatrogeny
- Segmental bone loss requiring specific therapy (bone transport, large structural allograft, megaprosthesis, etc)
- Vascular or neural injury
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 |
|---|---|---|
| Implantation of bone substitute plus autologous cultured mesenchymal cellsImplantation surgery of a synthetic bone substitute associated with autologous bone marrow cells expanded | Biological | Implantation surgery |
Primary outcome
Complication rate as percentage of patients with local complications regarding the non-union treatment in the follow-up
Time frame: At 6 weeks, 12 weeks, 24 weeks and 52 weeks after the implantation surgery
5 secondary outcomes
Number of patients with proven bone healing
Time frame: 6 weeks, 12 weeks, and 24 weeks after the implantation surgery
Amount of radiological callus
Time frame: 6 weeks, 12 weeks, and 24 weeks after the implantation surgery
Clinical consolidation
Time frame: 6 weeks, 12 weeks, and 24 weeks after implantation surgery
No reoperation done or scheduled
Time frame: 24 weeks after implantation surgery
Changes in serum levels of bone turnover markers
Time frame: 6 weeks, 12 weeks, and 24 weeks after the implantation surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- Results publication: PubMed 29598897Gomez-Barrena E, Rosset P, Gebhard F, Hernigou P, Baldini N, Rouard H, Sensebe L, Gonzalo-Daganzo RM, Giordano R, Padilla-Eguiluz N, Garcia-Rey E, Cordero-Ampuero J, Rubio-Suarez JC, Stanovici J, Ehrnthaller C, Huber-Lang M, Flouzat-Lachaniette CH, Chevallier N, Donati DM, Ciapetti G, Fleury S, Fernandez MN, Cabrera JR, Avendano-Sola C, Montemurro T, Panaitescu C, Veronesi E, Rojewski MT, Lotfi R, Dominici M, Schrezenmeier H, Layrolle P. Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial. Biomaterials. 2019 Mar;196:100-108. doi: 10.1016/j.biomaterials.2018.03.033. Epub 2018 Mar 19.
- Results publication: PubMed 28744314Granchi D, Gomez-Barrena E, Rojewski M, Rosset P, Layrolle P, Spazzoli B, Donati DM, Ciapetti G. Changes of Bone Turnover Markers in Long Bone Nonunions Treated with a Regenerative Approach. Stem Cells Int. 2017;2017:3674045. doi: 10.1155/2017/3674045. Epub 2017 Jun 20.
- Related InfoLink provided by the sponsor.
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.
Enrique Gomez Barrena principal investigator
Universidad Autonoma de Madrid
5 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Implantation of bone substitute plus autologous cultured mesenchymal cells in people with Delayed Union After Fracture of Humerus, Tibial or Femur, run by Institut National de la Santé Et de la Recherche Médicale, France at 5 sites in 4 countries.
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 6 inclusion and 18 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: finished, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in France, Germany, Italy, Spain. 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. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Complication rate as percentage of patients with local complications regarding the non-union treatment in the follow-up (time frame: At 6 weeks, 12 weeks, 24 weeks and 52 weeks after the implantation surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01842477, which also lists 2 linked publications.
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 4 Jun 2026; AzTrials last refreshed its copy on 8 Nov 2026.