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NCT Number: NCT03315702

Effect of Mechanical Ventilation on Plasma Concentration Level of R-spondin Proteins

As novel agonists of Wnt/β-catenin signaling pathway, R-spondin proteins constitute a class of ligands, including R-spondin 1/2/3/4, functioning through their receptors leucine-rich repeat-containing G-protein coupled receptor (LGR)4/5/6 to enhance Wnt/β-catenin activity. Since Wnt signaling plays pivotal roles in the regulation of many life processes involved in embryogenesis and adulthood, R-spondin proteins also take part in cell proliferation, differentiation and morphogenesis.For example, in the formation of respiratory system，R-spondin 2 is required for normal laryngeal-tracheal and lung morphogenesis，and the lack of R-spondin 1 expression results in the absence of duct side-branching development and subsequent alveolar formation. In addition, R-spondins show protective effect in tissue injury and diseases. R-spondin 1 and R-spondin 3 have been reported to prevent chemotherapy- or radiotherapy-induced mucous membrane lesion. R-spondin 1 attenuates oral mucositis contributed by radiotherapy in mouse models and R-spondin 3 potentiates intestinal regeneration elicited via gastrointestinal toxic effect of chemoradiotherapy treatment. However, whether R-spondin proteins exert salient influence on acute lung injury especially induced by mechanical ventilation is deficient. Therefore, this study aims to ascertain the implication of R-spondin proteins in the pathology of mechanical ventilation induced lung injury through detecting human plasma concentration change of R-spondin 1/2/3/4 after mechanical ventilation and interference effects in mouse model, which is helpful for prevention and treatment of ventilation induced lung injury.

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Key information

Conditions

Acute Lung Injury Lung Diseases Lung Injury Respiratory Tract Diseases Thoracic Injuries Wounds and Injuries

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Department of Anesthesia, Shanghai Xinhua hospital

Shanghai, Shanghai Municipality, 200082, China

About this study

Mechanical ventilation is a critical intervention for patients with acute respiratory failure. However, lung overdistension induced by mechanical ventilation also causes pulmonary endothelial dysfunction. The injurious effect of mechanical stretch on pulmonary endothelium has been implicated in the development of ventilator-induced lung injury, which is characterized by pulmonary inflammation and particularly increased vascular permeability. In addition, the investigators and others have previously shown that mechanical stretch increases cultured lung endothelial monolayer permeability in vitro and promotes lung vascular permeability in mice Thus, elucidating the mechanisms underlying the mechanical stretch-induced lung endothelial barrier dysfunction may provide a novel clinical therapeutic target against ventilator-induced lung injury.

As novel agonists of Wnt/β-catenin signaling pathway, R-spondin proteins constitute a class of ligands, including R-spondin 1/2/3/4, functioning through their receptors leucine-rich repeat-containing G-protein coupled receptor (LGR)4/5/6 to enhance Wnt/β-catenin activity. Since Wnt signaling plays pivotal roles in the regulation of many life processes involved in embryogenesis and adulthood, R-spondin proteins also take part in cell proliferation, differentiation and morphogenesis. For example, in the formation of respiratory system，R-spondin 2 is required for normal laryngeal-tracheal and lung morphogenesis，and the lack of R-spondin 1 expression results in the absence of duct side-branching development and subsequent alveolar formation. In addition, R-spondins show protective effect in tissue injury and diseases. R-spondin 1 and R-spondin 3 have been reported to prevent chemotherapy- or radiotherapy-induced mucous membrane lesion. R-spondin 1 attenuates oral mucositis contributed by radiotherapy in mouse models and R-spondin 3 potentiates intestinal regeneration elicited via gastrointestinal toxic effect of chemoradiotherapy treatment. However, whether R-spondin proteins exert salient influence on acute lung injury especially induced by mechanical ventilation is deficient. Therefore, this study aims to ascertain the implication of R-spondin proteins in the pathology of mechanical ventilation induced lung injury through detecting human plasma concentration change of R-spondin 1/2/3/4 after mechanical ventilation and interference effects in mouse model, which is helpful for prevention and treatment of ventilation induced lung injury.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • undergo elective surgery with mechanical ventilation lasting for > 3 hours; classified as physical status I to III according to the American Society of Anesthesiologists Physical Status Classification System; Written informed consent is approved.

Exclusion criteria

  • chronic lung disease; recent lung infection; recent anaesthetics or mechanical ventilation treatment; hemodilution with massive fluid supply during surgery; children；women during pregnancy or lactation; being involved in other clinical subjects

Treatment and study plan

Mechanical ventilation

Other

mechanical ventilation protocol: tidal volume 6-8 ml/kg, positive end-expiratory pressure 5 cm H2O, oxygen concentration 40%; respiratory rate 10-15/min, inspiratory/expiratory ratio 1:1.5.

Primary outcomes

  1. Change in Plasma Concentration of R-spondin 1

    Time frame: 3 hours

    The venous blood samples were collected twice for each patient that the first time was around the onset of the mechanical ventilation and the second was 3rd hour after the onset of the mechanical ventilation, which were named as sample A and sample B relatively. Then, plasmids were separated by centrifugation and detected for R-spondin1 concentration. And the outcome was calculated by subtracting the R-spondin1 plasmid concentration of sample A from the R-spondin1 plasmid concentration of sample B, which was the change in plasma concentration of R-spondin1.

  2. Change in Plasma Concentration of R-spondin 2

    Time frame: 3 hours

    The venous blood samples were collected twice for each patient that the first time was around the onset of the mechanical ventilation and the second was 3rd hour after the onset of the mechanical ventilation, which were named as sample A and sample B relatively. Then, plasmids were separated by centrifugation and detected for R-spondin2 concentration. And the outcome was calculated by subtracting the R-spondin2 plasmid concentration of sample A from the R-spondin2 plasmid concentration of sample B, which was the change in plasma concentration of R-spondin2.

  3. Change in Plasma Concentration of R-spondin3

    Time frame: 3 hours

    The venous blood samples were collected twice for each patient that the first time was around the onset of the mechanical ventilation and the second was 3rd hour after the onset of the mechanical ventilation, which were named as sample A and sample B relatively. Then, plasmids were separated by centrifugation and detected for R-spondin3 concentration. And the outcome was calculated by subtracting the R-spondin3 plasmid concentration of sample A from the R-spondin3 plasmid concentration of sample B, which was the change in plasma concentration of R-spondin3.

  4. Change in Plasma Concentration of R-spondin4

    Time frame: 3 hours

    The venous blood samples were collected twice for each patient that the first time was around the onset of the mechanical ventilation and the second was 3rd hour after the onset of the mechanical ventilation, which were named as sample A and sample B relatively. Then, plasmids were separated by centrifugation and detected for R-spondin4 concentration. And the outcome was calculated by subtracting the R-spondin4 plasmid concentration of sample A from the R-spondin4 plasmid concentration of sample B, which was the change in plasma concentration of R-spondin4.

Sponsors and collaborators

Lead sponsor

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Other

Registry information

Official study title

the Change of R-spondin Proteins Plasma Concentration Level Caused by Mechanical Ventilation and Its Effect on Mechanical Ventilation Induced Lung Injury

Important dates

Study start
2017
Primary completion
2017
Study completion
2017
First posted
Oct 20, 2017
Registry last updated
Jul 25, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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