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

Surgical Site Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04897971
• Other study ID #: 20-2946
• Status: Enrolling by invitation
• Start date: August 24, 2021
• Est. completion date: May 2026

Study information

• Verified date: April 2024
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 200
• Est. completion date: May 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Orthopedic Procedures
• Spine
• Staphylococcal Infections
• Staphylococcus Aureus Infection
• Surgical Site Infection
• Surgical Wound Infection

Intervention

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

Locations

Country	Name	City	State
United States	Univeristy of Colorado Denver	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	University of Rochester

Country where clinical trial is conducted

United States, 

References & Publications (3)

Muthukrishnan G, Soin S, Beck CA, Grier A, Brodell JD Jr, Lee CC, Ackert-Bicknell CL, Lee FE, Schwarz EM, Daiss JL. A Bioinformatic Approach to Utilize a Patient's Antibody-Secreting Cells against Staphylococcus aureus to Detect Challenging Musculoskeletal Infections. Immunohorizons. 2020 Jun 22;4(6):339-351. doi: 10.4049/immunohorizons.2000024. — View Citation

Nishitani K, Beck CA, Rosenberg AF, Kates SL, Schwarz EM, Daiss JL. A Diagnostic Serum Antibody Test for Patients With Staphylococcus aureus Osteomyelitis. Clin Orthop Relat Res. 2015 Sep;473(9):2735-49. doi: 10.1007/s11999-015-4354-2. Epub 2015 May 27. — View Citation

Oh I, Muthukrishnan G, Ninomiya MJ, Brodell JD Jr, Smith BL, Lee CC, Gill SR, Beck CA, Schwarz EM, Daiss JL. Tracking Anti-Staphylococcus aureus Antibodies Produced In Vivo and Ex Vivo during Foot Salvage Therapy for Diabetic Foot Infections Reveals Prognostic Insights and Evidence of Diversified Humoral Immunity. Infect Immun. 2018 Nov 20;86(12):e00629-18. doi: 10.1128/IAI.00629-18. Print 2018 Dec. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The percentage of Staphylococcus aureus spine implant associated infections correctly identified by "medium enriched for newly synthesized antibodies" (MENSA)	"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
Primary	Change "Medium enriched for newly synthesized antibodies" (MENSA) titers in the post-operative period	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
Primary	"Medium enriched for newly synthesized antibodies" (MENSA) titers in spine implant infections compared to S. aureus infections of other orthopedic site infections.	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	Confirmation of Staphylococcus aureus in spine implant associated infection by polymerase chain reaction (PCR)	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