Clinical trial NCT06371950: Gut Microbiome in Orthopaedics
Official title: Gut Microbiome in Orthopaedics: Effect of Probiotics on Initial Implant Migration and Joint Inflammation After Total Knee Replacement
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Total Knee Arthroplasty
Inflammation
Gastrointestinal Health
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2024-04-17
Enrollment: 0
Sex: FEMALE
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Implant Migration
timeFrame: baseline, 6 weeks
Secondary outcomes:
measure: Bone Density
timeFrame: baseline, 6 weeks
measure: Magnitude of 18-F-Fluoroethyl(2-(2-fluoroethoxy)phenyl)-proprionate ([¹⁸F]FEPPA) Tracer Uptake
timeFrame: 6 weeks
Other outcomes:
measure: Veterans Rand 12-Item Health Survey (VR-12)
timeFrame: pre-operative, 6 weeks
measure: EuroQol-5D (EQ-5D)
timeFrame: pre-operative, 6 weeks
measure: Western Ontario McMaster Osteoarthritis Index (WOMAC)
timeFrame: pre-operative, 6 weeks
measure: Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP)
timeFrame: pre-operative, 6 weeks
measure: Patient Global Assessment (PGA)
timeFrame: pre-operative, 6 weeks
measure: University of California, Los Angeles (UCLA) Activity Score
timeFrame: pre-operative, 6 weeks
measure: Oxford Knee Score - English for Canada
timeFrame: pre-operative, 6 weeks
measure: Knee Society Score (KSS)
timeFrame: pre-operative, 6 weeks
measure: Presence of MRSA
timeFrame: pre-operative, 6 weeks
measure: Microbial Diversity - Taxonomic Differences
timeFrame: pre-operative, 6 weeks
measure: Microbial Diversity - Taxonomic Correlation
timeFrame: pre-operative, 6 weeks
measure: Diet and Supplement Questionnaire
timeFrame: pre-operative
measure: Histopathology
timeFrame: intraoperative
measure: Immunohistochemistry
timeFrame: intraoperative
measure: Inflammatory Blood Marker: C-Reactive Protein
timeFrame: pre-operative, 6 weeks
measure: Inflammatory Blood Marker: Interleukin-1B
timeFrame: pre-operative, 6 weeks
measure: Inflammatory Blood Marker: Interleukin-6
timeFrame: pre-operative, 6 weeks
measure: Inflammatory Blood Marker: Interleukin-8
timeFrame: pre-operative, 6 weeks
measure: Inflammatory Blood Marker: Tumor Necrosis Factor Alpha
timeFrame: pre-operative, 6 weeks
measure: Inflammatory Blood Marker: Erythrocyte Sedimentation Rate
timeFrame: pre-operative, 6 weeks
measure: Inflammatory Blood Marker: Alkaline Phosphatase
timeFrame: pre-operative, 6 weeks
measure: Inflammatory Blood Marker: Calcium
timeFrame: pre-operative, 6 weeks
measure: Inflammatory Blood Marker: Albumin
timeFrame: pre-operative, 6 weeks
measure: Inflammatory Blood Marker: Urate
timeFrame: pre-operative, 6 weeks
measure: Inflammatory Blood Marker: Total Protein
timeFrame: pre-operative, 6 weeks
measure: Inflammatory Blood Marker: Creatinine
timeFrame: pre-operative, 6 weeks
measure: Inflammatory Blood Marker: Vitamin D
timeFrame: pre-operative, 6 weeks
measure: Inflammatory Blood Marker: White Blood Cell Count
timeFrame: pre-operative, 6 weeks
measure: Inflammatory Blood Marker: Red Blood Cell Count
timeFrame: pre-operative, 6 weeks
measure: Inflammatory Blood Marker: Hemoglobin Concentration
timeFrame: pre-operative, 6 weeks
measure: Inflammatory Blood Marker: Hematocrit Percentage
timeFrame: pre-operative, 6 weeks
measure: Inflammatory Blood Marker: Platelet Count
timeFrame: pre-operative, 6 weeks
Locations:
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
Study officials:
affiliation: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: Brent Lanting, BESc, MD
role: PRINCIPAL_INVESTIGATOR
References: