Clinical trial NCT06658379: Prospective Validation Study of the CD8+TEMRA Cells As a Prognostic Biomarker of Healing Outcome After Fracture
Official title: Prospective Validation Study of the CD8+TEMRA Cells As a Prognostic Biomarker of Healing Outcome After Fracture
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Fracture Non Union
Fracture Healing
Long Bone Delayed-Union Fracture
Humerus Shaft Fracture
Forearm Fracture
Femoral Neck Fractures
Femur Distal Fracture
Pertrochanteric Fracture of Femur
Femoral Shaft Fracture
Proximal Tibia Fracture
Tibial Shaft Fracture
Distal Tibia Fracture
Keywords: long bone fracture
impaired fracture healing
fracture non-union
prognosis
prognostic biomarker
Immune system
T cells
radiology
bone fracture healing
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Unfallkrankenhaus Berlin
name: Vivantes Klinikum Spandau
name: University Hospital Dresden
name: Universitaetsklinikum Muenster
name: Leipzig University Hospital
name: Jena University Hospital
name: Beckman Coulter, Inc.
name: Federal Ministry of Education and Reserach (BMBF)
First posted: 2024-10-26
Enrollment: 640
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
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

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* 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).

Primary outcomes:
measure: Clinical assessement of the fracture consolidation at first study endpoint based on radiological images
timeFrame: From surgery to 19 weeks post surgery
Secondary outcomes:
measure: clinical assessement of the fracture consolidation at second study endpoint based on radiological images
timeFrame: From surgery to 36 weeks post surgery
Other outcomes:
measure: Ability to work
timeFrame: From surgery to 1 year post surgery
measure: Proportion of subjects with an additional intervention independent of a surgical or non-surgical treatment to foster the fracture healing process
timeFrame: From surgery to 1 year post surgery
measure: Duration of Physiotherapy
timeFrame: From surgery to 1 year post surgery
measure: Weight bearing and fracture healing
timeFrame: From surgery to 1 year post surgery
measure: Rehabilitation and fracture healing
timeFrame: From surgery to 1 year post surgery
measure: Infection rate
timeFrame: From surgery to 1 year post surgery
Locations:
city: Münster
country: Germany
facility: Clinic for Trauma, Hand and Reconstructive Surgery University Hospital Münster (UKM)
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: University Hospital University Centre for Orthopaedics and Trauma Surgery Dresden
state: Sachsen
city: Leipzig
country: Germany
facility: University Hospital Clinic and Polyclinic for Orthopaedics, Trauma Surgery and Plastic Surgery Leipzig
state: Sachsen
city: Eisenberg
country: Germany
facility: Clinic for Orthopaedics and Trauma Surgery Jena/Eisenberg
state: Thüringen
city: Berlin
country: Germany
facility: Unfallkrankenhaus Berlin
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin, Centre for Musculoskeletal Surgery (CMSC)
city: Berlin
country: Germany
facility: Vivantes Klinikum Spandau Berlin
Study officials:
affiliation: Charité Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT)
name: Simon Reinke, Phd
role: PRINCIPAL_INVESTIGATOR
References: