PTP1B Implication in the Vascular Dysfunction Associated With Obstructive Sleep Apnea

Not Applicable

Completed

• Conditions: Sleep Apnea; Atherosclerosis; Inflammation
• Interventions: Other: myeloid PTP1B expression analysis

• Registration Number: NCT04235023
• Lead Sponsor: University Hospital, Angers

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-01-07
• Study First Submitted QC: 2020-01-17
• Study First Posted: 2020-01-21
• Study Start: 2020-02-04
• Primary Completion: 2022-02-03
• Study Completion: 2022-02-03
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-10
• Last Update Posted: 2024-06-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 58

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
non OSA patients	myeloid PTP1B expression analysis	30 patients investigated for suspected OSA with an apnea hypopnea index \< 15 per hour
OSA patients	myeloid PTP1B expression analysis	30 patients investigated for suspected OSA with an apnea hypopnea index ≥ 15 per hour

Primary Outcome Measures

Name	Time	Method
myeloid PTP1B expression	baseline	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.
myeloid PTP1B activity	baseline	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.

Secondary Outcome Measures

Name	Time	Method
in vitro PTP1B implication on macrophage inflammatory response	baseline	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.
PTP1B exosomal expression.	baseline	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.

Trial Locations

Locations (1)

Angers University Hospital; 🇫🇷 Angers, France