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

NCT06658379 | Recruiting DMC

• 2 other identifiers: 01EK1514DRKS00010872
• Study Type: observational
• Target: 640
• Locations: 1 country
• Sites: 7

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.

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

Outcome Measures

Primary Outcomes (1)

• 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

  From surgery to 19 weeks post surgery

Secondary Outcomes (1)

• clinical assessement of the fracture consolidation at second study endpoint based on radiological images

  From surgery to 36 weeks post surgery

Other Outcomes (6)

• Ability to work

  From surgery to 1 year post surgery

• Proportion of subjects with an additional intervention independent of a surgical or non-surgical treatment to foster the fracture healing process

  From surgery to 1 year post surgery

• Duration of Physiotherapy

  From surgery to 1 year post surgery

Study Arms (1)

fracture cohort

Humerus fracture, forearm fracture, femoral fracture. tibia fracture

Diagnostic Test: CD8+TEMRA

Interventions

CD8+TEMRA DIAGNOSTIC_TEST

fracture cohort

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Unfallkrankenhaus Berlin: collaborator
• Vivantes Klinikum Spandau: collaborator
• University Hospital Dresden: collaborator
• Universitaetsklinikum Muenster: collaborator
• Leipzig University Hospital: collaborator
• Jena University Hospital: collaborator
• Beckman Coulter, Inc.: collaborator
• Federal Ministry of Education and Reserach (BMBF): collaborator

Study Sites (7)

Clinic for Trauma, Hand and Reconstructive Surgery University Hospital Münster (UKM)

Münster, North Rhine-Westphalia, 48149, Germany

RECRUITING

University Hospital University Centre for Orthopaedics and Trauma Surgery Dresden

Dresden, Saxony, 01307, Germany

RECRUITING

University Hospital Clinic and Polyclinic for Orthopaedics, Trauma Surgery and Plastic Surgery Leipzig

Leipzig, Saxony, 04103, Germany

RECRUITING

Unfallkrankenhaus Berlin

Berlin, State of Berlin, 12683, Germany

RECRUITING

Charité Universitätsmedizin Berlin, Centre for Musculoskeletal Surgery (CMSC)

Berlin, State of Berlin, 13353, Germany

RECRUITING

Vivantes Klinikum Spandau Berlin

Berlin, State of Berlin, 13585, Germany

RECRUITING

Clinic for Orthopaedics and Trauma Surgery Jena/Eisenberg

Eisenberg, Thuringia, 07607, Germany

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

blood samples

MeSH Terms

Conditions

Fractures, Ununited; Femoral Neck Fractures; Femoral Fractures, Distal

Condition Hierarchy (Ancestors)

Fractures, Bone; Wounds and Injuries; Hip Fractures; Femoral Fractures; Hip Injuries; Leg Injuries

Study Officials

• Simon Reinke, Phd

  Charité Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Simon Reinke, Phd

CONTACT

+49 (0)30-450-659617; simon.reinke@bih-charite.de

Sven Geißler, Phd

CONTACT

+49(0)30450 559539; sven.geissler@bih-charite.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of BIH Core Unit Cell and Tissue Harvesting

Study Record Dates

• First Submitted: October 17, 2024
• First Posted: October 26, 2024
• Study Start: December 1, 2016
• Primary Completion: April 1, 2025
• Study Completion: June 1, 2025
• Last Updated: October 26, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (7)