Gut Microbiome in Orthopaedics: Revision Total Knee Arthroplasty (GUMBO)

September 15, 2025 updated by: Brent Lanting, London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Gut Microbiome in Orthopaedics: Investigating the Role of Gut Microbiome Composition in Total Knee Arthroplasty Failure

Many patients who receive knee replacement surgery must return for a revision (or repeat) surgery due to ongoing pain, stiffness, infection, or implant loosening. The role of the gut microbiome-the collection of bacteria and other microbes within the human gastrointestinal tract-is just beginning to be recognized in orthopaedics. The gut microbiome has been found to affect the immune response and bone regulation, potentially contributing to infection or loosening after total joint replacement. Antibiotics are regularly used in orthopaedic surgery to reduce the risk of infection, yet they might also harm gut microbiota and reduce their potentially beneficial effects. As a result, understanding the relationship between gut microbiota and surgical outcomes has become increasingly important. Therefore, this study aims to determine if there are differences in gut microbiota composition between patients with well-functioning knee replacements and those requiring revision knee replacements. Additional study aims include assessing inflammation, implant loosening, metal ion levels, and circulating bacteria in blood or tissue between well-functioning or failed knee replacements.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

30

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • London, Ontario, Canada, N6A5A5
        • University Hospital
        • Contact:
        • Principal Investigator:
          • Brent Lanting, MD, MSc, FRCSC

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients at University Hospital scheduled to undergo a revision TKA.

Description

Inclusion Criteria:

  • Scheduled to undergo a revision TKA
  • Willing and able to comply with follow-up requirements
  • Ability to provide informed consent
  • Ability to read, write, and speak English

Exclusion Criteria:

  • Pregnancy
  • Less than 3 months post-operation from primary surgery
  • Diagnosis of periprosthetic fracture
  • Scheduled for DAIR (debridement, antibiotics, and implant retention) revision surgery
  • Scheduled for stage 2 PJI revision

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Revision TKA
Participants scheduled to undergo a revision TKA will be recruited. They must be more than 3 months post-operation from their primary surgery, and the revision must be for something other than periprosthetic fracture, DAIR (debridement, antibiotics, and implant retention), or stage 2 periprosthetic joint infection.
Procedure: Revision Total Knee Arthroplasty
Study participants must be scheduled to receive a revision TKA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gut Microbiome Composition
Time Frame: Gut microbiome composition will be assessed pre-operatively and at 5 days and 6 weeks post-operation to determine how it changes post-operation.
The gut microbiome composition of the revision total knee arthroplasty (TKA) cohort prior to revision surgery will be compared to that of the well-functioning TKA cohort. Additionally, we will evaluate changes in the gut microbiome within the revision cohort from before surgery to six weeks after surgery.
Gut microbiome composition will be assessed pre-operatively and at 5 days and 6 weeks post-operation to determine how it changes post-operation.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Inducible Displacement Measurements with Weight-Bearing Computed Tomography (WBCT)
Time Frame: WBCT exams will be performed at one timepoint prior to the study participant's revision surgery.
Seated and standing WBCT exams will be performed. The bone and implant will be segmented, and a novel software (WBCT-based radiostereometric analysis (WBCT-RSA)) will be used to measure implant motion between the double seated exams (precision) or seated and standing exams (inducible displacement). Change in implant position will be measured in millimeters as maximum total point motion (MTPM). MTPM will be compared between the revision TKA cohort and a cohort with well-functioning implants.
WBCT exams will be performed at one timepoint prior to the study participant's revision surgery.
Inflammation in the Knee Joint Based on [18F]FEPPA Standard Uptake Values (SUV)
Time Frame: PET/CT exams will be performed at one timepoint prior to the study participant's revision surgery.
Positron Emission Tomography/Computed Tomography (PET/CT) of the knee joint will be performed using the radiotracer [18F]FEPPA, which binds to molecules highly expressed on inflammatory cells. Radiotracer uptake will be quantified using SUV. SUV near the bone and joint will be calculated and compared between the revision TKA cohort and the well-functioning TKA cohort.
PET/CT exams will be performed at one timepoint prior to the study participant's revision surgery.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Inducible Displacement and Microbiome Composition
Time Frame: Inducible displacement exams will be performed pre-operatively and will be compared to the gut microbiome from pre-operation to 6 weeks post-operation, and to the intra-operative joint microbiome.
Joint and gut microbiome composition, along with inducible displacement measurements, will be assessed to determine whether alterations in the gut microbiome lead to increased within-bone implant motion.
Inducible displacement exams will be performed pre-operatively and will be compared to the gut microbiome from pre-operation to 6 weeks post-operation, and to the intra-operative joint microbiome.
Implant Wear Volume and Within-Bone Implant Motion from Inducible Displacement Exams
Time Frame: Inducible displacement exams will be performed pre-operatively and will be compared to the amount of wear that has occurred on implants retrieved during revision surgery.
Seated and standing WBCT exams will be performed. The bone and implant will be segmented, and a novel software (WBCT-RSA) will be used to measure implant motion between the seated and standing exams (inducible displacement). Change in implant position will be measured in millimeters as MTPM. An optical coordinate measuring machine will be used to quantitatively measure the amount of volume loss from the retrieved implant components. Inducible displacement MTPM will be compared to volume loss to determine if greater within-bone implant motion may cause greater wear of the implant component resulting in more volume loss.
Inducible displacement exams will be performed pre-operatively and will be compared to the amount of wear that has occurred on implants retrieved during revision surgery.
Metal Ion Levels and Within-Bone Implant Motion from Inducible Displacement Exams
Time Frame: Inducible displacement exams will be performed pre-operatively and will be compared to the amount of circulating metal ions pre-operation.
Seated and standing WBCT exams will be performed. The bone and implant will be segmented, and a novel software (WBCT-RSA) will be used to measure implant motion between the seated and standing exams (inducible displacement). Change in implant position will be measured in millimeters as MTPM. Metal ion levels (cobalt, chromium, nickel, and titanium) will be measured from a blood draw prior to the revision surgery. Inducible displacement MTPM and metal ion levels will be compared to determine if greater within-bone implant motion causes greater levels of circulating metal ions.
Inducible displacement exams will be performed pre-operatively and will be compared to the amount of circulating metal ions pre-operation.
[18F]FEPPA Activity and Microbiome Composition
Time Frame: PET/CT exams will be performed pre-operatively and will be compared to the gut microbiome from pre-operation to 6 weeks post-operation, and to the intra-operative joint microbiome.
Joint and gut microbiome composition will be compared to [18F]FEPPA activity, to assess whether alterations in the gut microbiome contribute to increased inflammation in the knee joint.
PET/CT exams will be performed pre-operatively and will be compared to the gut microbiome from pre-operation to 6 weeks post-operation, and to the intra-operative joint microbiome.
[18F]FEPPA Activity and Implant Wear Volume
Time Frame: PET/CT exams will be performed pre-operatively and will be compared to the amount of wear that has occurred on implants retrieved during revision surgery.
[18F]FEPPA activity from PET/CT will be used to detect the amount of inflammation present in the knee joint. An optical coordinate measuring machine will be used to quantitatively measure the amount of volume loss from the retrieved implant components as an indicator of wear. The relationship between volume loss and [18F]FEPPA activity will be assessed.
PET/CT exams will be performed pre-operatively and will be compared to the amount of wear that has occurred on implants retrieved during revision surgery.
[18F]FEPPA Activity and Metal Ion Levels
Time Frame: PET/CT exams will be performed pre-operatively and will be compared to the amount of circulating metal ions pre-operation.
[18F]FEPPA activity from PET/CT will be used to detect the amount of inflammation present in the knee joint. Metal ion levels (cobalt, chromium, nickel, and titanium) will be measured pre-operatively and the relationship between inflammation and circulating metal ions will be assessed.
PET/CT exams will be performed pre-operatively and will be compared to the amount of circulating metal ions pre-operation.

Collaborators and Investigators

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

Sponsor

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Investigators

  • Principal Investigator: Brent Lanting, MD, MSc, FRCSC, Schulich School of Medicine & Dentistry

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 (Estimated)

October 1, 2025

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

April 7, 2025

First Submitted That Met QC Criteria

April 22, 2025

First Posted (Actual)

April 30, 2025

Study Record Updates

Last Update Posted (Estimated)

September 19, 2025

Last Update Submitted That Met QC Criteria

September 15, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 126857

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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