Fracture Non UnionBioBoneNCT06658379
Prospective Validation Study of the CD8+TEMRA Cells As a Prognostic Biomarker of Healing Outcome After Fracture
An observational study of Fracture Non Union and Fracture Healing, run by Charite University, Berlin, Germany at 7 sites in Germany.
Trial summary
In approx. 10-15% of all fracture patients, there is a prolonged healing time or even a complete absence of fracture healing (non-union). As a result, these patients require further surgical interventions, combined with renewed or prolonged hospitalisation/rehabilitation and incapacity to work. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Fracture Non Union, Fracture Healing, Long Bone Delayed-Union Fracture
- What is being tested?
- CD8+TEMRA
- How many people
- 640 participants
- Where
- 7 sitesGermany
- Study dates
- Dec 2016to Jun 2025
- Phase
- Observational
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: University Hospital UniversityCentre for Orthopaedics and Trauma Surgery Dresden Charité Universitätsmedizin Berlin Centre for Musculoskeletal Surgery Clinic for Orthopaedics and Trauma Surgery Jena/Eisenberg Clinic Trauma Hospital Berlin Berlin Vivantes Hospital Spandau Berlin Clinic University Hospital Clinic and Polyclinic for Orthopaedics, Trauma Surgery and Plastic Surgery Leipzig
Who may be able to join
- male or female subjects
- subjects > 18 to 80 years of age at the time of screening
- closed fractures
- fractures of the humerus-shaft, forearm-shaft, femur and tibia
- Subjects suffering monotrauma or comparable with monotrauma, due to comparable post-surgery mobilisation
- osteosynthesis
- subject has signed an informed consent form
- legal capacity
Who cannot join
- cancer related fractures
- periprosthetic fractures
- known active Hepatitis B virus or Hepatitis C virus infection at screening
- known human immunodeficiency virus (HIV) infection, severe uncontrolled inflammatory disease or severe uncontrolled autoimmune disease (e.g., ulcerative colitis, Crohn's disease
- active malignancy or history of malignancy within 5 years prior to screening
- known diagnosis of moderate to severe dementia based on subject's medical history or severe psychiatric disorder
Show all 13Show fewer
- known history of drug or alcohol abuse in the past 12 months, based on self-report or medical record
- history of autologous/allogeneic bone marrow (BM) or solid organ transplantation
- exposure to allogeneic cell-based therapy in the past or exposure to autologous cell therapy in the last 12 months before screening
- pregnancy
- subject is currently enrolled in an investigational device or drug trial, or has not yet completed a period of at least 30 days since ending other investigational device or drug trial(s).
- subject is detained or institutionalized under a court order or administrative order
- in the opinion of the investigator, the subject is unsuitable for participating in the study (patient compliance).
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Germany7 sites, 7 recruiting
- Recruiting
Unfallkrankenhaus Berlin
Berlin, State of Berlin, 12683
Regina Zappel, MD, +49 (0) 30 5681 4050, kristina.zappel@ukb.de
Stefan Weber, MD
- Recruiting
Charité Universitätsmedizin Berlin, Centre for Musculoskeletal Surgery (CMSC)
Berlin, State of Berlin, 13353
Sven Märdian, Prof., +4930450552092, sven.maerdian@charite.de
Sven Märdian, Prof.
- Recruiting
Vivantes Klinikum Spandau Berlin
Berlin, State of Berlin, 13585
Anja Bauer, MD, +4930130132290, anjamaria.bauer@vivantes.de
Philipp Schwabe, MD
- Recruiting
University Hospital University Centre for Orthopaedics and Trauma Surgery Dresden
Dresden, Saxony, 01307
Maik Stiehler, Prof., Phd, +49351 458-3777, Maik.Stiehler@ukdd.de
Maik Stiehler, Prof., Phd
- Recruiting
Clinic for Orthopaedics and Trauma Surgery Jena/Eisenberg
Eisenberg, Thuringia, 07607
Georg Matziolis, Prof., +4936691 81010, g.matziolis@waldkliniken-eisenberg.de
Georg Matziolis, Prof.
- Recruiting
University Hospital Clinic and Polyclinic for Orthopaedics, Trauma Surgery and Plastic Surgery Leipzig
Leipzig, Saxony, 04103
Georg Osterhoff, Prof, +49 341 97-17867, georg.osterhoff@medizin.uni-leipzig.de
Georg Osterhoff, Prof.
- Recruiting
Clinic for Trauma, Hand and Reconstructive Surgery University Hospital Münster (UKM)
Münster, North Rhine-Westphalia, 48149
Marion Laumann, +49251 83-51479, marion.laumann@ukmuenster.de
Richard Stange, Prof.
About this study
In approx. 10-15% of all fracture patients, there is a prolonged healing time or even a complete absence of fracture healing (non-union). As a result, these patients require further surgical interventions, combined with renewed or prolonged hospitalisation/rehabilitation and incapacity to work. To summarise, this therefore represents a serious socio-economic problem. At present, there is no prognostic method for the early prediction of patients at risk of a disturbed healing process. However, if these patients are successfully stratified, there are already a variety of therapeutic strategies available to additionally stimulate fracture healing. Therefore, the aim is to conduct a prospective clinical study to validate CD8+ TEMRA cells as a prognostic marker of impaired fracture healing. The investigators assume that preoperative CD8+ TEMRA cell expression represents a prognostic biomarker with high diagnostic precision for differentiating between a) normal healing patients, b) delayed healing patients and c) pseudarthrosis patients. Furthermore, the sensitivity and specificity should be high enough, health-economically significant and realisable in clinical routine.
Read the detailed description
The aim is to identify high-risk patients before the initial operation based on their immunological profile and to be able to provide them with an improved, individualised therapeutic strategy. There are already a large number of approved therapeutic options that are currently only used in revision cases because, among other things, preoperative diagnostics and prognostics are lacking. Furthermore, a sufficient preoperatively determined biomarker would form the basis for the development of new therapeutic approaches, which represent a low cost-benefit and risk-benefit ratio.
The prospective biomarker validation study is applied in a routine-adapted procedure, i.e. all visits are part of the clinical radiological and functional routine checks. Blood sampling on arrival at the hospital will be used to determine the preoperative value of CD8+TEMRA cells. The healing process will be recorded using X-ray/CT images, radiological scores and functional clinical examinations as well as the SF-36. The 1st study endpoint (delayed healing) is after 17-19 weeks postoperatively, the 2nd study endpoint (pseudarthrosis) after 34-36 weeks. The validation of the biomarker will take place in a blinded procedure, whereby the predefined threshold value of the preoperative CD8+ TEMRA cell expression will be compared with the patient's healing status.
- Conditions
- Fracture Non Union, Fracture Healing, Long Bone Delayed-Union Fracture, Humerus Shaft Fracture, Forearm Fracture, Femoral Neck Fractures
- Being tested
- CD8+TEMRA
- Keywords
- long bone fracture, impaired fracture healing, fracture non-union, prognosis, prognostic biomarker, Immune system, T cells, radiology, bone fracture healing
- Medical subject headings
- Fractures, Ununited, Femoral Neck Fractures, Femoral Fractures, Distal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD8+TEMRADiagnostic test
| Study group | Role | What they receive |
|---|---|---|
| fracture cohort | Humerus fracture, forearm fracture, femoral fracture. tibia fracture Receives: Diagnostic Test: CD8+TEMRA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical assessement of the fracture consolidation at first study endpoint based on radiological images
Clinical assessement of the fracture consolidation (yes/no) based on radiological images at primary end point
Measured: From surgery to 19 weeks post surgery
Secondary outcomes (1)
clinical assessement of the fracture consolidation at second study endpoint based on radiological images
fracture consolidation (yes/no) after 36 weeks post surgery based on radiological images.
Measured: From surgery to 36 weeks post surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2024
- Study startDec 2016
- Primary completionApr 2025 (estimated)
- Study completionJun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fracture Non UnionStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 640 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Collaborators
- Unfallkrankenhaus Berlin, Vivantes Klinikum Spandau, University Hospital Dresden, Universitaetsklinikum Muenster, Leipzig University Hospital, Jena University Hospital, Beckman Coulter, Inc., Federal Ministry of Education and Reserach (BMBF)
- Responsible party
- Principal investigator, Dr. Simon Reinke, Charite University, Berlin, Germany
- Investigators
- Simon Reinke, Phd, Principal investigator, Charité Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06658379
- Sponsor's protocol ID
- 01EK1514
- Other IDs
- DRKS00010872
- Acronym
- BioBone
- Status last verified
- Oct 2024
- First submitted
- 17 Oct 2024
- Last updated
- 26 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: For data protection reasons, no individual participant data will be shared
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Validation Study of the CD8+TEMRA Cells As a Prognostic Biomarker of Healing Outcome After Fracture
- ClinicalTrials.gov ID
- NCT06658379
- Acronym / sponsor ID
- BioBone / 01EK1514
- Conditions
- Fracture Non Union, Fracture Healing, Long Bone Delayed-Union Fracture, Humerus Shaft Fracture, Forearm Fracture, Femoral Neck Fractures
- Keywords
- long bone fracture, impaired fracture healing, fracture non-union, prognosis, prognostic biomarker, Immune system, T cells, radiology
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 640 participants (estimated)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Collaborators
- Unfallkrankenhaus Berlin, Vivantes Klinikum Spandau, University Hospital Dresden, Universitaetsklinikum Muenster, Leipzig University Hospital, Jena University Hospital, Beckman Coulter, Inc., Federal Ministry of Education and Reserach (BMBF)
- Study start
- Dec 2016 (actual)
- Primary completion
- Apr 2025 (estimated)
- Study completion
- Jun 2025 (estimated)
- First posted
- 26 Oct 2024 (actual)
- 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.
In approx. 10-15% of all fracture patients, there is a prolonged healing time or even a complete absence of fracture healing (non-union). As a result, these patients require further surgical interventions, combined with renewed or prolonged hospitalisation/rehabilitation and incapacity to work. To summarise, this therefore represents a serious socio-economic problem. At present, there is no prognostic method for the early prediction of patients at risk of a disturbed healing process. However, if these patients are successfully stratified, there are already a variety of therapeutic strategies available to additionally stimulate fracture healing. Therefore, the aim is to conduct a prospective clinical study to validate CD8+ TEMRA cells as a prognostic marker of impaired fracture healing. The investigators assume that preoperative CD8+ TEMRA cell expression represents a prognostic biomarker with high diagnostic precision for differentiating between a) normal healing patients, b) delayed healing patients and c) pseudarthrosis patients. Furthermore, the sensitivity and specificity should be high enough, health-economically significant and realisable in clinical routine.
Detailed description
The aim is to identify high-risk patients before the initial operation based on their immunological profile and to be able to provide them with an improved, individualised therapeutic strategy. There are already a large number of approved therapeutic options that are currently only used in revision cases because, among other things, preoperative diagnostics and prognostics are lacking. Furthermore, a sufficient preoperatively determined biomarker would form the basis for the development of new therapeutic approaches, which represent a low cost-benefit and risk-benefit ratio.
The prospective biomarker validation study is applied in a routine-adapted procedure, i.e. all visits are part of the clinical radiological and functional routine checks. Blood sampling on arrival at the hospital will be used to determine the preoperative value of CD8+TEMRA cells. The healing process will be recorded using X-ray/CT images, radiological scores and functional clinical examinations as well as the SF-36. The 1st study endpoint (delayed healing) is after 17-19 weeks postoperatively, the 2nd study endpoint (pseudarthrosis) after 34-36 weeks. The validation of the biomarker will take place in a blinded procedure, whereby the predefined threshold value of the preoperative CD8+ TEMRA cell expression will be compared with the patient's healing status.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| fracture cohort | – | Diagnostic Test: CD8+TEMRAHumerus fracture, forearm fracture, femoral fracture. tibia fracture |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- University Hospital UniversityCentre for Orthopaedics and Trauma Surgery Dresden Charité Universitätsmedizin Berlin Centre for Musculoskeletal Surgery Clinic for Orthopaedics and Trauma Surgery Jena/Eisenberg Clinic Trauma Hospital Berlin Berlin Vivantes Hospital Spandau Berlin Clinic University Hospital Clinic and Polyclinic for Orthopaedics, Trauma Surgery and Plastic Surgery Leipzig
Key inclusion criteria (8 listed)
- male or female subjects
- subjects > 18 to 80 years of age at the time of screening
- closed fractures
- fractures of the humerus-shaft, forearm-shaft, femur and tibia
- Subjects suffering monotrauma or comparable with monotrauma, due to comparable post-surgery mobilisation
Key exclusion criteria (13 listed)
- cancer related fractures
- periprosthetic fractures
- known active Hepatitis B virus or Hepatitis C virus infection at screening
- known human immunodeficiency virus (HIV) infection, severe uncontrolled inflammatory disease or severe uncontrolled autoimmune disease (e.g., ulcerative colitis, Crohn's disease
- active malignancy or history of malignancy within 5 years prior to screening
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 |
|---|---|---|
| CD8+TEMRA | Diagnostic test | fracture cohort |
Primary outcome
Clinical assessement of the fracture consolidation at first study endpoint based on radiological images
Time frame: From surgery to 19 weeks post surgery
Clinical assessement of the fracture consolidation (yes/no) based on radiological images at primary end point
1 secondary outcome
clinical assessement of the fracture consolidation at second study endpoint based on radiological images
Time frame: From surgery to 36 weeks post surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2024.
- Individual participant dataSharing planned: No. For data protection reasons, no individual participant data will be shared
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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.
Simon Reinke, Phd principal investigator
Charité Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT)
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Fracture Non Union and Fracture Healing, run by Charite University, Berlin, Germany at 7 sites in Germany.
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 8 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 26 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Germany. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Simon Reinke, Phd (+49 (0)30-450-659617, simon.reinke@bih-charite.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical assessement of the fracture consolidation at first study endpoint based on radiological images (time frame: From surgery to 19 weeks post surgery). 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 26 Oct 2024.