Microfluidic Organotypic Model for Monocyte Transendothelial Migration to the Joint in Obese Osteoarthritic Patients (MOTEM)

Development of a Microfluidic Organotypic Model to Evaluate Monocyte Transendothelial Migration to the Joint in Obese Osteoarthritic Patients

Osteoarthritis (OA) is the fastest growing cause of disability worldwide due to population ageing and increasing obesity incidence. Obese individuals have a higher risk of OA insurgence and severe progression due to several risk factors, including their systemic inflammation state and superior migratory ability of monocytes. In the present project we aim at the development of a novel 3D microfluidic organotypic model resembling the joint to investigate the migration ability of monocytes from obese and non-obese OA patients.

We hypothesize that monocytes from obese OA patients display superior migration ability and a specific pattern of chemokine surface receptors compared to monocytes from non-obese OA patients. We also hypothesize that these features lead to a superior infiltration of monocytes/macrophages to the synovial membrane in obese OA patients. Based on this, our main aim will be to highlight differences between Mo from obese and non-obese OA patients in terms of surface receptors and migration ability in a microfluidic organotypic model.

Study Overview

• Status: Unknown
• Conditions: Osteoarthritis
• Intervention / Treatment: Other: use of patient-derived biological samples

• Study Type: Observational
• Enrollment (Anticipated): 88

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

OA patients undergoing prosthetic surgery at IRCCS Istituto Ortopedico Galeazzi

Description

Inclusion criteria

Obese OA patients

• Subscription of informed consent
• BMI ≥ 30
• age between 60-80 years included
• Kelgrenn-Lawrence equal or superior to grade III
• presence of synovitis
• patients undergoing knee replacement
• suspension of NSAIDs from one week before the surgical procedure according to the standard clinical practice

Non-obese OA patients

• Subscription of informed consent
• BMI ≤ 28
• age between 60-80 years included
• Kelgrenn-Lawrence equal or superior to grade III
• presence of synovitis
• patients undergoing knee replacement
• suspension of NSAIDs from one week before the surgical procedure according to the standard clinical practice

Exclusion criteria

Obese OA patients - HCV, HIV, HBV, TPHA infection

Non-obese OA patients

- HCV, HIV, HBV, TPHA infection

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
obese OA patients; Use of patient-derived biological samples Inclusion Criteria: Subscription of informed consent; BMI ≥ 30; age between 60-80 years included; Kelgrenn-Lawrence equal or superior to grade III; presence of synovitis; patients undergoing knee replacement; suspension of NSAIDs from one week before the surgical procedure according to the standard clinical practice Exclusion criteria: - HCV, HIV, HBV, TPHA infection	Other: use of patient-derived biological samples; We will use biological samples that are routinely collected as waste material from patients undergoing prosthetic surgery at IRCCS Istituto Ortopedico Galeazzi. Peripheral blood will be also collected from patients during the pre-surgery visit and during the post-surgery hospitalization coinciding with routine blood sample collection.
Non-obese OA patients; Use of patient-derived biological samples Inclusion criteria: Subscription of informed consent; BMI ≤ 28; age between 60-80 years included; Kelgrenn-Lawrence equal or superior to grade III; presence of synovitis; patients undergoing knee replacement; suspension of NSAIDs from one week before the surgical procedure according to the standard clinical practice Exclusion criteria: - HCV, HIV, HBV, TPHA infection	Other: use of patient-derived biological samples; We will use biological samples that are routinely collected as waste material from patients undergoing prosthetic surgery at IRCCS Istituto Ortopedico Galeazzi. Peripheral blood will be also collected from patients during the pre-surgery visit and during the post-surgery hospitalization coinciding with routine blood sample collection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chemokine receptor expression	To evaluate and compare the expression of chemokine surface receptors on monocytes from obese and non-obese OA patients.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monocyte transendothelial migration	To monitor the transendothelial migration of monocytes from OA patients in response to chemokines present in the synovial fluid using a microfluidic organotypic model.	48 hours

Collaborators and Investigators

• Sponsor: Istituto Ortopedico Galeazzi

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2017
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): July 1, 2019

Study Registration Dates

• First Submitted: November 15, 2017
• First Submitted That Met QC Criteria: November 15, 2017
• First Posted (Actual): November 20, 2017

Study Record Updates

• Last Update Posted (Actual): November 20, 2017
• Last Update Submitted That Met QC Criteria: November 15, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: MOTEM

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No