Staphylococcus Aureus InfectionNCT04897971
Serum Based Diagnosis of and Monitoring of Infection Recovery in Orthopedic Spine Implant Infections
An observational study of Staphylococcus Aureus Infection and Surgical Site Infection, run by University of Colorado, Denver at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Staphylococcus Aureus Infection, Surgical Site Infection, Orthopedic Procedures
- What is being tested?
- Medium enriched for newly synthesized antibodies in spine infection
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Aug 2021to May 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Univeristy of Colorado Denver
Aurora, Colorado, 80045
About this study
Official title: 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.
Read the 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.
- Being tested
- Medium enriched for newly synthesized antibodies in spine infection
- Keywords
- Spine, Orthopedic Implant infection
- Medical subject headings
- Staphylococcal Infections, Surgical Wound Infection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Medium enriched for newly synthesized antibodies in spine infectionDiagnostic 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
| Study group | Role | What they receive |
|---|---|---|
| Spine implant associated infection cohort | Adult patients undergoing revision spine surgeries with suspected infection of previous instrumentation. Receives: Diagnostic Test: Medium enriched for newly synthesized antibodies in spine infection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Baseline
Secondary outcomes (1)
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.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2021
- Study start24 Aug 2021
- Primary completionMay 2026 (estimated)
- Study completionMay 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Staphylococcus Aureus InfectionStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- University of Rochester
- Responsible party
- Sponsor
- Investigators
- Cheryl L Ackert-Bicknell, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04897971
- Sponsor's protocol ID
- 20-2946
- Status last verified
- Apr 2024
- First submitted
- 18 May 2021
- Last updated
- 3 Apr 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32571786Oh 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.
PubMed 30275008Nishitani 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.
PubMed 26013151
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of MENSA to Improve the Diagnosis of Causative Infectious Agent and Monitor Infection Recovery in Orthopedic Spine Infection
- ClinicalTrials.gov ID
- NCT04897971
- Acronym / sponsor ID
- 20-2946
- Keywords
- Spine, Orthopedic Implant infection
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- University of Rochester
- Study start
- 24 Aug 2021 (actual)
- Primary completion
- May 2026 (estimated)
- Study completion
- May 2026 (estimated)
- First posted
- 24 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Spine implant associated infection cohort | – | Diagnostic Test: Medium enriched for newly synthesized antibodies in spine infectionAdult patients undergoing revision spine surgeries with suspected infection of previous instrumentation. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Medium enriched for newly synthesized antibodies in spine infectionMedium enriched for newly synthesized antibodies titers in patients with Staphylococcus aureus infections of orthopedic spine implants at baseline and in the post operative period | Diagnostic test | Spine implant associated infection cohort |
Primary outcome
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.
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.
"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.
1 secondary outcome
Confirmation of Staphylococcus aureus in spine implant associated infection by polymerase chain reaction (PCR)
Time frame: Baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2024.
- Background: PubMed 32571786Muthukrishnan 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.
- Background: PubMed 30275008Oh 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.
- Background: PubMed 26013151Nishitani 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cheryl L Ackert-Bicknell, PhD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Staphylococcus Aureus Infection and Surgical Site Infection, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The percentage of Staphylococcus aureus spine implant associated infections correctly identified by "medium enriched for newly synthesized antibodies" (MENSA) (time frame: Baseline). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04897971, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2024.