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

NCT04897971 | Enrolling By Invitation

• 1 other identifier: 20-2946
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Staphylococcus Aureus Infection; Surgical Site Infection; Orthopedic Procedures; Spine

Keywords

Spine, Orthopedic Implant infection

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• "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 Outcomes (1)

• Confirmation of Staphylococcus aureus in spine implant associated infection by polymerase chain reaction (PCR)

  Baseline

Study Arms (1)

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

Interventions

Medium enriched for newly synthesized antibodies in spine infection DIAGNOSTIC_TEST

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

Spine implant associated infection cohort

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• University of Rochester: collaborator

Study Sites (1)

Univeristy of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Related 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.

  PMID: 32571786 BACKGROUND

• 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.

  PMID: 30275008 BACKGROUND

• 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.

  PMID: 26013151 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

1. No more than two, 1-gram (\~ 2 cm3, total) pieces of surgical discard tissue will be collected from the area around the orthopedic implants. 2. 5-10 mL of whole blood drawn into a 10 mL heparinized collection tube fort he purpose of collecting peripheral blood mono nuclear cells. 3. 1-2 mL of whole blood drawn for preparing serum

MeSH Terms

Conditions

Staphylococcal Infections; Surgical Wound Infection

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Wound Infection; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Cheryl L Ackert-Bicknell, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2021
• First Posted: May 24, 2021
• Study Start: August 24, 2021
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: April 3, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)