PTP1B Implication in the Vascular Dysfunction Associated With Obstructive Sleep Apnea (MacroSAS)

Obstructive sleep apnea (OSA) syndrome is associated with increased vascular dysfunction and atherosclerosis. Especially, it has been shown that OSA associated intermittent hypoxia represents a pro inflammatory stimulus resulting in macrophage polarization.

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling pathways involved in atherosclerosis. It has been shown that myeloid PTP1B deficiency protects against atherosclerosis.

As hypoxia has also been shown to increase PTP1B expression and activity, this study will evaluate the myeloid PTP1B expression and activity in patients with OSA as compared to controls and will investigate myeloid PTP1B involvement in the vascular pro inflammatory precess described in OSA.

Study Overview

• Status: Completed
• Conditions: Inflammation; Atherosclerosis; Sleep Apnea
• Intervention / Treatment: Other: myeloid PTP1B expression analysis

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Angers, France, 49100
    • Angers University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Overnight polysomnographic recording for suspected OSA
• Apnea hypopnea index ≥ 15 per hour for OSA patients
• Apnea hypopnea index < 15 per hour for non OSA patients

Exclusion Criteria:

• past history of cardiovascular diseases
• diabetes
• dyslipidemia
• hypertension
• obesity (body mass index > 35 kg/m2
• past history or ongoing inflammatory diseases
• cognition impairment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: OSA patients; 30 patients investigated for suspected OSA with an apnea hypopnea index ≥ 15 per hour	Other: myeloid PTP1B expression analysis; peripheral blood macrophage PTP1B expression
OTHER: non OSA patients; 30 patients investigated for suspected OSA with an apnea hypopnea index < 15 per hour	Other: myeloid PTP1B expression analysis; peripheral blood macrophage PTP1B expression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
myeloid PTP1B expression	Peripheral blood will be collected from OSA and non OSA patients. Macrophage will be isolated by specific centrifugation. PTP1B expression will be assessed by Western Blot.	baseline
myeloid PTP1B activity	Peripheral blood will be collected from OSA and non OSA patients. Macrophage will be isolated by specific centrifugation. PTP1B activity will be assessed by specific colorimetric assay.	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PTP1B exosomal expression.	Peripheral blood will be collected from OSA and non OSA patients. Exosomes will be isolated by consecutive centrifugations. PTP1B expression will be assessed by Western Blot.	baseline
in vitro PTP1B implication on macrophage inflammatory response	Macrophage isolated from patients will be stimulated by pro inflammatory agents (IL6, TNF alpha) in the presence and absence of PTP1B inhibitor (MSI-1436). The inflammatory response will be assessed by measuring inflammatory cytokines in the supernatant by ELISA.	baseline

Collaborators and Investigators

• Sponsor: University Hospital, Angers
• Investigators: Principal Investigator: Wojciech Trzepizur, MD Ph D, Angers University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 4, 2020
• Primary Completion (ACTUAL): February 3, 2022
• Study Completion (ACTUAL): February 3, 2022

Study Registration Dates

• First Submitted: January 7, 2020
• First Submitted That Met QC Criteria: January 17, 2020
• First Posted (ACTUAL): January 21, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 13, 2023
• Last Update Submitted That Met QC Criteria: February 9, 2023
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: macrophage; PTP1B
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Respiratory Tract Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Inflammation; Apnea; Atherosclerosis
• Other Study ID Numbers: 49RC19-0226

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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