Gut Microbiome in Orthopaedics: Revision Total Knee Arthroplasty

NCT06951477 | Not Yet Recruiting

• 1 other identifier: 126857
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Revision Total Knee Arthroplasty; Osteoarthritis, Knee

Keywords

Revision TKA; Gut Microbiome; Implant Loosening; Inflammation; Weight-Bearing Computed Tomography; PET/CT

Outcome Measures

Primary Outcomes (1)

• Gut Microbiome Composition

  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 Outcomes (2)

• Inducible Displacement Measurements with Weight-Bearing Computed Tomography (WBCT)

  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)

  PET/CT exams will be performed at one timepoint prior to the study participant's revision surgery.

Other Outcomes (6)

• Inducible Displacement and Microbiome Composition

  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

  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

  Inducible displacement exams will be performed pre-operatively and will be compared to the amount of circulating metal ions pre-operation.

Study Arms (1)

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

Interventions

Revision Total Knee Arthroplasty PROCEDURE

Study participants must be scheduled to receive a revision TKA.

Revision TKA

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients at University Hospital scheduled to undergo a revision TKA.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

University Hospital

London, Ontario, N6A5A5, Canada

Location

Related Publications (13)

• Hext RA, Kaptein BL, Howard JL, Lanting BA, Teeter MG. Inducible displacement of cementless total knee arthroplasty components with conventional and weight-bearing CT-based radiostereometric analysis. J Orthop Res. 2025 Mar;43(3):640-649. doi: 10.1002/jor.26017. Epub 2024 Nov 15.

  PMID: 39545647 BACKGROUND

• Xiao PL, Hsu CJ, Ma YG, Liu D, Peng R, Xu XH, Lu HD. Prevalence and treatment rate of osteoporosis in patients undergoing total knee and hip arthroplasty: a systematic review and meta-analysis. Arch Osteoporos. 2022 Jan 14;17(1):16. doi: 10.1007/s11657-021-01055-9.

  PMID: 35029750 BACKGROUND

• Li J, Ho WTP, Liu C, Chow SK, Ip M, Yu J, Wong HS, Cheung WH, Sung JJY, Wong RMY. The role of gut microbiota in bone homeostasis. Bone Joint Res. 2021 Jan;10(1):51-59. doi: 10.1302/2046-3758.101.BJR-2020-0273.R1.

  PMID: 33448869 BACKGROUND

• Hernandez CJ, Yang X, Ji G, Niu Y, Sethuraman AS, Koressel J, Shirley M, Fields MW, Chyou S, Li TM, Luna M, Callahan RL, Ross FP, Lu TT, Brito IL, Carli AV, Bostrom MPG. Disruption of the Gut Microbiome Increases the Risk of Periprosthetic Joint Infection in Mice. Clin Orthop Relat Res. 2019 Nov;477(11):2588-2598. doi: 10.1097/CORR.0000000000000851.

  PMID: 31283731 BACKGROUND

• Chisari E, D'Mello D, Sherman MB, Parvizi J. Inflammatory Bowel Diseases Increase the Risk of Periprosthetic Joint Infection. J Bone Joint Surg Am. 2022 Jan 19;104(2):160-165. doi: 10.2106/JBJS.20.01585.

  PMID: 34648464 BACKGROUND

• Hernandez CJ. Musculoskeletal Microbiology: The Microbiome in Orthopaedic Biomechanics. Curr Opin Biomed Eng. 2021 Sep;19:100290. doi: 10.1016/j.cobme.2021.100290. Epub 2021 May 6.

  PMID: 34151053 BACKGROUND

• Moran MM, Wessman P, Rolfson O, Bohl DD, Karrholm J, Keshavarzian A, Sumner DR. The risk of revision following total hip arthroplasty in patients with inflammatory bowel disease, a registry based study. PLoS One. 2021 Nov 4;16(11):e0257310. doi: 10.1371/journal.pone.0257310. eCollection 2021.

  PMID: 34735461 BACKGROUND

• Abdeen A, Della Valle CJ, Kendoff D, Chen AF. The Paradox of Prosthetic Joint Infection and the Microbiome: Are Some Bacteria Actually Helpful? Arthroplast Today. 2022 Jan 18;13:116-119. doi: 10.1016/j.artd.2021.11.011. eCollection 2022 Feb.

  PMID: 35106346 BACKGROUND

• Chisari E, Wouthuyzen-Bakker M, Friedrich AW, Parvizi J. The relation between the gut microbiome and osteoarthritis: A systematic review of literature. PLoS One. 2021 Dec 16;16(12):e0261353. doi: 10.1371/journal.pone.0261353. eCollection 2021.

  PMID: 34914764 BACKGROUND

• Hernandez CJ. Musculoskeletal microbiology: The utility of the microbiome in orthopedics. J Orthop Res. 2021 Feb;39(2):251-257. doi: 10.1002/jor.24927. Epub 2020 Dec 7.

  PMID: 33245146 BACKGROUND

• Boer CG, Radjabzadeh D, Medina-Gomez C, Garmaeva S, Schiphof D, Arp P, Koet T, Kurilshikov A, Fu J, Ikram MA, Bierma-Zeinstra S, Uitterlinden AG, Kraaij R, Zhernakova A, van Meurs JBJ. Intestinal microbiome composition and its relation to joint pain and inflammation. Nat Commun. 2019 Oct 25;10(1):4881. doi: 10.1038/s41467-019-12873-4.

  PMID: 31653850 BACKGROUND

• Moran MM, Wilson BM, Li J, Engen PA, Naqib A, Green SJ, Virdi AS, Plaas A, Forsyth CB, Keshavarzian A, Sumner DR. The gut microbiota may be a novel pathogenic mechanism in loosening of orthopedic implants in rats. FASEB J. 2020 Nov;34(11):14302-14317. doi: 10.1096/fj.202001364R. Epub 2020 Sep 15.

  PMID: 32931052 BACKGROUND

• Bourdon CE, Koudys ZJ, Lanting BA, Appleton CT, Thiessen JD, Teeter MG. Attenuation correction for PET/MRI to measure tracer activity surrounding total knee arthroplasty. Eur J Hybrid Imaging. 2022 Nov 7;6(1):31. doi: 10.1186/s41824-022-00152-3.

  PMID: 36336748 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

We will collect stool samples pre-operatively and at 5 days and 6 weeks post-operatively. Microbial DNA will be extracted from the stool samples and metagenomic sequencing will be performed.

MeSH Terms

Conditions

Osteoarthritis, Knee; Inflammation

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Brent Lanting, MD, MSc, FRCSC

  Schulich School of Medicine & Dentistry

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brent Lanting, MD, MSc, FRCSC

CONTACT

519-685-8500; Brent.Lanting@lhsc.on.ca

Lyndsay Somerville, PhD

CONTACT

519-685-8500; Lyndsay.Somerville@lhsc.on.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Orthopaedic Surgeon

Study Record Dates

• First Submitted: April 7, 2025
• First Posted: April 30, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)