Cytokine Profiles and suPAR in Spondylodiscitis

August 9, 2019 updated by: Ayla Yagdiran, University of Cologne

Verification and Progress of Cytokine Profiles and suPAR for the Discrimination of Infectious and Non-infectious, Degenerative Diseases of the Spine

Spondylodiscitis is an infectious disease of the intervertebral discs and adjacent vertebral bodies, which often has a protracted progression. Diagnosis is frequently delayed because of the unspecific pathology and a lack of specific infection markers. However, an early diagnosis is fundamental to prevent long periods with symptoms including extensive back pain and progressive and destructive changes of the spine.

Cytokines can be helpful to extend the knowledge about diverse biological processes. Furthermore, they are a promising category of biomarkers that are already present in the early phases of developing diseases. Currently, little is known about the participation of cytokines in Spondylodiscitis. The aim of this study is to establish a non-invasive method to improve the diagnosis of spondylodiscitis. Therefore, blood and tissue samples will be analyzed at different time points for the concentration of specific cytokines to select potential marker cytokines via a Multiplex Assay and suPAR (soluble urokinase-type plasminogen activator receptor) via ELISA. After successful identification of the biomarkers cytokines and suPAR, verification of the results will be done by expression analysis of cytokine-producing cells.

The potential of such a diagnostic method lies in reducing medical costs and preventing extensive pain and structural changes of the spine.

Experimental research will be performed with the approval of the ethic committee of the medical faculty of the University of Cologne.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Spondylodiscitis is a primary infection of the intervertebral discs with secondary infection of the adjacent end-plates and vertebral bodies. It is relatively rare with an incidence of 2.4:100.000 and three times more common among men. The process of infection, which is commonly creeping, leads to a destruction of the vertebral bodies and production of abscesses, which can cause neurological deficits.

Clinical symptoms, especially in the early stages, are uncommon. Patients suffer from unspecific back pain and fever occurs only in 50% of all cases. Currently, markers used including leucocyte count, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are also unspecific.For this reason of that several weeks may elapse between the first signs of symptoms and the final diagnosis of spondylodiscitis. Therefore, the identification of the pathogen is indispensable for an effective antibiotic therapy.

Spinal infections are generally monomicrobial, frequently with a haematogenous source. Therefore, blood cultures can be used for identifying the pathogens. In case of negative blood cultures, the pathogens can be identified by invasive methods such as percutaneous punch biopsy or CT-guided fine needle aspiration. Despite biopsies, the pathogen can only be identified in two out of three patients. Failures of pathogen identification are mainly due to previous systemic antibiotic treatment. As a consequence, diagnosis is often based on medical imaging methods (CT, MRT, PET, radiograph, skeletal scintigraphy). The disadvantage of these methods is that structural changes of the spine must occur to become visible.

Treatment of an advanced spondylodiscitis consists of removal of the necrotic tissue, stabilization of the affected vertebral bodies and concomitant antibiotic therapy. Randomized studies for the duration of antibiotic treatments have not been published as yet. Current recommendations are between 6 to 12 weeks. For evaluating the therapy response only the clinical improvement and the CRP value are used. The mean period of stay in the hospital is about 49 days.

The goal is to establish a non-invasive method which allows discrimination of infectious and non-infectious diseases to improve the diagnosis of spondylodiscitis. For that purpose, blood and tissue samples from patients with spondylodiscitis and erosive osteochondrosis will be collected and analyzed for their cytokine and suPAR concentration. Erosive osteochondrosis is a non-infectious, degenerative disease of the spine with similar surgical treatment. Thus, it is an optimal reference group. Nevertheless, erosive osteochondrosis includes special types, called modic type I-III. Because modic type I is associated with an immune response caused by repeated traumata of the spine this modic type will be excluded from the study.

Cytokines are messengers, which are present in blood and all tissues, regulating the immune response. In this study, the goal is to assess if cytokine profiles and suPAR contribute to the discrimination of infectious and non-infectious spondylodiscitis and if this could be verified by the characterization of the cytokine-producing cells. Furthermore, the investigators want to analyze the therapy response by measuring the cytokine and suPAR profiles.

Routine blood collection will be carried out directly before surgery and also during the stationary hospitalization on day 4 and day 10. Additional blood collection will be done after 6 weeks and 3 months during the follow-up. At each time point serum and plasma will be used for the study to determine the cytokine and suPAR concentration and expression of the cytokine-producing cells. Necrotic tissue, which is removed during the surgery, will be analyzed microbiologically as well as pathologically. Parts of this tissue will also be used for the determination of cytokines. Further blood samples will be collected when a patient appears again in the Department of Orthopaedic Surgery and Traumatology because of treatment and therapy of a re-infection. A minimum of 15 patients per group - control group (erosive osteochondrosis modic type II-III) and spondylodiscitis - will be included in this study. Both groups should be homogeneous in sex and age distribution.

There will be no additional pain or complications for the patients participating in this study. All samples will be collected for a period of about one year and stored at -80°C. Afterwards, the blood and tissue samples will be analyzed for potential marker suPAR via ELISA and cytokines by using a Multiplex Assay. Furthermore, results will be linked to anamnesis to detect potential correlations. Specific correlations can indicate a diagnostic and perhaps a prognostic value of the measured cytokines and suPAR.

Study Type

Observational

Enrollment (Actual)

36

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • NRW
      • Cologne, NRW, Germany, 50931
        • Studienzentrum Orthopädie & Unfallchirurgie

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients with spondylodiscitis, erosive osteochondrosis

Description

Inclusion Criteria:

  • Existence of an informed consent
  • Legal competence of the patient
  • Lumbar and thoracic spine pathology with an indication of spondylodiscitis or rather erosive osteochondrosis
  • Surgical stabilization of the affected lumbar and thoracic vertebral bodies and a removal of the affected intervertebral discs

Exclusion Criteria:

• Patients with autoimmune diseases, chronic infections (HIV, hepatitis B and C), acute infections of other parts besides the spine and active cancer diseases

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Other
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Spondylodiscitis
vertebral osteomyelitis, erosive osteochondrose
Other: Cytokine Profile and suPAR
Routine blood collection will be carried out directly before surgery and also during the stationary hospitalization on day 4 and day 10. Additional blood collection will be done after 6 weeks and 3 months during the follow-up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with high cytokine and suPAR profiles as a measurement for the diagnosis of spondylodiscitis
Time Frame: Change from Baseline in different Cytokine and suPAR profiles to 3 month after surgery
different cytokine and suPAR profiles between groups
Change from Baseline in different Cytokine and suPAR profiles to 3 month after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with high cytokine and suPAR profiles as a measurement for the diagnosis of vertebral osteomyelitis
Time Frame: Change from Baseline in different Cytokine and suPAR profiles to 3 month after surgery
cytokines and suPAR in tissues/cells
Change from Baseline in different Cytokine and suPAR profiles to 3 month after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Cologne

Investigators

  • Principal Investigator: Jan Siewe, Dr. med., University Hospital, Department of Orthopaedic Surgery and Traumatology,

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2015

Primary Completion (Actual)

June 1, 2017

Study Completion (Actual)

August 1, 2017

Study Registration Dates

First Submitted

September 15, 2015

First Submitted That Met QC Criteria

September 17, 2015

First Posted (Estimate)

September 18, 2015

Study Record Updates

Last Update Posted (Actual)

August 13, 2019

Last Update Submitted That Met QC Criteria

August 9, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Uni-Köln_11_2014

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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