Prospective Validation Study of the CD8+TEMRA Cells As a Prognostic Biomarker of Healing Outcome After Fracture (BioBone)

Charité University Medicine Berlin

Status

Enrolling

Conditions

Forearm Fracture

Fracture Healing

Femoral Neck Fractures

Femoral Shaft Fracture

Long Bone Delayed-Union Fracture

Proximal Tibia Fracture

Pertrochanteric Fracture of Femur

Fracture Non Union

Distal Tibia Fracture

Tibial Shaft Fracture

Humerus Shaft Fracture

Femur Distal Fracture

Treatments

Diagnostic Test: CD8+TEMRA

Study type

Observational

Funder types

Other

Industry

Identifiers

NCT06658379

01EK1514

DRKS00010872 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

640 estimated patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

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).