Serum Based Diagnosis of and Monitoring of Infection Recovery in Orthopedic Spine Implant Infections

April 2, 2024 updated by: University of Colorado, Denver

Use of MENSA to Improve the Diagnosis of Causative Infectious Agent and Monitor Infection Recovery in Orthopedic Spine Infection

The goal of this study is to test a new way to diagnose and track treatment of spine infections caused by the bacteria Staphylococcus aureus.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

Ongoing Staphylococcus aureus (S. aureus) infections of the spine associated with orthopedic hardware implants elicit prominent immune responses against a repertoire of proteins characteristic of the invading pathogen. Antibodies specific for these antigens can be measured in the serum or in a novel sample created by culturing circulating Antibody Secreting Cells (ASC) in vitro where they create an analytic fluid called here "medium enriched for newly synthesized antibodies" (MENSA). The hypothesis of this study addresses three essential attributes of this analytic approach that can yield both a valuable tool for research on spinal infections and in the future, this can be developed a clinical tool for diagnosis and monitoring of therapeutic success in patients. By measuring the emergence of these signature antibodies in the serum and/or MENSA, the goals of this study are: 1) To differentiate between patients with an ongoing S. aureus infections, not just "general infection, in the spine using only blood samples; 2) To track the success (or failure) of therapeutic interventions; and 3) to distinguish spinal infections from S. aureus infections in other sites by the repertoire of antibodies that are elicited.

Study Type

Observational

Enrollment (Estimated)

200

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

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Univeristy of Colorado Denver

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

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients undergoing revision spine surgeries at the University of Colorado Hospital. with suspected infection of previous instrumentation will be offered enrollment. The enrolled patients will be identified prior to surgery by the surgeons and research staff through radiographs and images contained in the medical records and the parameters of suspected infection which include:

  • Blood biomarkers: elevated C-reactive protein (CRP) and ESR (erythrocyte sedimentation rate), and white blood cell count
  • X-ray imaging: to show osteolysis and possibly implant-loosening
  • MRI or CT imaging: looking for fluid accumulations, evidence of inflammation, enhancements.

Description

Inclusion Criteria:

  • patients with known or suspected spinal infections associated with spinal orthopedic implant(s);
  • patients over 18 years of age and younger than 85;
  • patients undergoing spinal revision surgery.

Exclusion Criteria:

  • Diagnosed as immuno-compromised or immuno-suppressed based on medication use;
  • On-going or previously diagnosed musculoskeletal infections associated non-spine hardware (e.g., prosthetic hip, prosthetic knee, prosthetic shoulder);
  • Current diabetic foot ulcer/infection;
  • Patients undergoing cancer treatment (including radiation and chemotherapies);
  • Pregnancy;
  • Absence of a spleen;
  • Over the age of 85 or under the age of 18.
  • Weigh less than 110 pounds, or for which it would otherwise be unsafe for them to undergo a blood draw.

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: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Spine implant associated infection cohort
Adult patients undergoing revision spine surgeries with suspected infection of previous instrumentation.
Diagnostic test: Medium enriched for newly synthesized antibodies in spine infection
Medium enriched for newly synthesized antibodies titers in patients with Staphylococcus aureus infections of orthopedic spine implants at baseline and in the post operative period

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The percentage of Staphylococcus aureus spine implant associated infections correctly identified by "medium enriched for newly synthesized antibodies" (MENSA)
Time Frame: Baseline
"A medium enriched for newly synthesized antibodies" (MENSA) is the supernatant collected from cultured antibody secreting cells. Peripheral blood monocytes (PBMCs) are washed and placed into cell culture. After 24 hours, the media contains a high concentration of newly made antibodies. This media is referred to as MENSA. This is tested to see if the antibodies collected react against a panel of antigens. MENSA immunoglobulin G (IgG) titers for each antigen will be assessed for their predictive ability to identify the presence of S. aureus in spine implant-associated infections using receiver operating characteristic (ROC) curve analysis (alone or in combination), with overall prediction accuracy summarized by the area-under-the-curve (AUC). Participants will then be categorized as Staphylococcus aureus (S. aureus) positive or negative based on MENSA. The percentage of correctly identified S. aureus determinations compared to clinical diagnosis will be determined.
Baseline
Change "Medium enriched for newly synthesized antibodies" (MENSA) titers in the post-operative period
Time Frame: 2 weeks, 6 weeks, 3 months, 6 months, 1 year and 2 years post-surgery
MENSA IgG titers (as defined in Outcome 1) will be measured at 2 weeks, 6 weeks, 3 months, 6 months, 1 year and 2 years post-surgery. A longitudinal measure of antibody activity defined as the average change per study visit from baseline will used to track infection clearance versus persistent infection. Levels of anti-S. aureus antibodies in MENSA should decline to background in patients whose infections have been successfully treated and remain elevated in those whose infections persist.
2 weeks, 6 weeks, 3 months, 6 months, 1 year and 2 years post-surgery
"Medium enriched for newly synthesized antibodies" (MENSA) titers in spine implant infections compared to S. aureus infections of other orthopedic site infections.
Time Frame: Baseline
MENSA IgG titers (as defined in Outcome 1) will be compared to responses measured in a pre-existing collection of samples from patients who had experienced: 1) prosthetic joint infections; 2) septic arthritis; 3) diabetic foot infections; 4) soft-tissue infections; and 5) fracture-related infections. The goal will be to identify a combination of antigens that is uniquely discriminatory for spine infections.
Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Confirmation of Staphylococcus aureus in spine implant associated infection by polymerase chain reaction (PCR)
Time Frame: Baseline
Total DNA will be collected from surgical discarded tissue from sites adjacent to the infection. polymerase chain reaction (PCR) using primers that amplify a region of the Staphylococcus aureus genome will be run to confirm the presence/absence of Staphylococcus aureus at the infection site.
Baseline

Collaborators and Investigators

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

Sponsor

University of Colorado, Denver

Collaborators

University of Rochester

Investigators

  • Principal Investigator: Cheryl L Ackert-Bicknell, PhD, University of Colorado, Denver

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)

August 24, 2021

Primary Completion (Estimated)

May 1, 2026

Study Completion (Estimated)

May 1, 2026

Study Registration Dates

First Submitted

May 18, 2021

First Submitted That Met QC Criteria

May 18, 2021

First Posted (Actual)

May 24, 2021

Study Record Updates

Last Update Posted (Actual)

April 3, 2024

Last Update Submitted That Met QC Criteria

April 2, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20-2946

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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