Gut Microbiome in Orthopaedics

Not Applicable

Withdrawn

• Conditions: Total Knee Arthroplasty; Inflammation; Gastrointestinal Health
• Interventions: Other: Placebo; Dietary Supplement: Probiotic Formula Bacillus subtilis

• Registration Number: NCT06371950
• Lead Sponsor: London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Brief Summary

Patients having knee replacement surgery regularly experience joint pain and compromised bone quality leading to implant loosening and periprosthetic fractures. The role of the gut microbiome, which is the collection of bacteria and other microbes within the human gastrointestinal tract, is just beginning to be recognized, including its potential effects on pain, infection, and loosening after total joint replacement. Antibiotics are regularly used in orthopaedic surgery to reduce the risk of infection, but they also harm gut microbiota and reduce their potentially beneficial effects. Probiotics may have a role to play in enhancing bone quality and decreasing synovial inflammation after joint replacement surgery, and this study will explore the potential relationship of probiotic use with implant migration, bone density, and patient outcomes.

This study is a randomized, controlled, double-blinded trial comparing probiotic use with placebo in post-menopausal women undergoing primary total knee replacement. The main questions it aims to answer are:

* to compare implant migration between groups from baseline to six weeks post-surgery

* to compare bone density and joint inflammation between groups from baseline to six weeks post-surgery

* to compare gut microbiome composition and patient-reported outcome measures between groups from baseline to six weeks post-surgery

Detailed Description

Participants will take a daily probiotic (DE111®) or placebo once daily starting 3 weeks prior to surgery until six weeks after surgery. The following will be completed at baseline and 6 weeks:

* Bloodwork

* Fecal sample collection

* MRSA swab

* Patient-reported outcome measures

* CT imaging scan

In addition, the following will be done:

* Intraoperative fluid and tissue collection

* Positron Emission Tomography-Magnetic Resonance Imaging (PET-MRI) scan at 6 weeks post-surgery

Researchers will compare the probiotic and placebo groups for any significant differences in implant stability, bone quality, inflammation, gut microbiome composition, and pain.

Study Timeline

• Study First Submitted: 2024-02-27
• Study First Submitted QC: 2024-04-12
• Study First Posted: 2024-04-17
• Study Start: 2025-01-01
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-13
• Last Update Posted: 2025-03-18
• Primary Completion: 2027-01-01
• Study Completion: 2028-01-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Female
• Target Recruitment: 30

Inclusion Criteria

• Signed informed consent obtained prior to any study-related activities
• Postmenopausal female patients of London Health Sciences Centre (LHSC) aged 55-75 years
• Scheduled to undergo primary total knee replacement for osteoarthritis

Exclusion Criteria

• Unable to understand and respond to the provided questionnaires
• Male sex
• Inflammatory arthritis
• Periprosthetic infection
• Prior surgery with hardware insertion in the target knee
• Metabolic syndrome
• Inflammatory bowel disease
• Body mass index <18.5 kg/m2
• Immune-compromised condition (e.g. AIDS, lymphoma, patients undergoing long-term corticosteroid treatment)
• Any contraindications for PET-MRI
• Allergy to cephalosporin antibiotics

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	1 capsule of placebo, to be taken once daily starting 3 weeks prior to surgery until 6 weeks after surgery.
Probiotic DE111®	Probiotic Formula Bacillus subtilis	1 capsule of probiotic DE111® containing 5 billion CFU Bacillus subtilis, to be taken once daily starting 3 weeks prior to surgery until 6 weeks after surgery.

Primary Outcome Measures

Name	Time	Method
Implant Migration	baseline, 6 weeks	Tibial component migration over time calculated by measuring the position of the component compared to the bone using CT imaging.

Secondary Outcome Measures

Name	Time	Method
Bone Density	baseline, 6 weeks	Volumetric bone mineral density over time measured in the anteromedial, anterolateral, posteromedial, and posterolateral regions surrounding the tibial component using CT imaging.
Magnitude of 18-F-Fluoroethyl(2-(2-fluoroethoxy)phenyl)-proprionate ([¹⁸F]FEPPA) Tracer Uptake	6 weeks	Magnitude of standardized uptake values (SUV) of the \[¹⁸F\]FEPPA tracer uptake in the synovium as measured by PET-MRI. SUV will be calculated using the mean signal intensity, body weight, and decay-corrected injected dose.

Trial Locations

Locations (1)

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada