The Role and Mechanism of O-GlcNAc Glycosylation Modified HAS2 in the Hyaluronic Acid Synthesis in ARDS

Sponsor

Southeast University, China (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05055557

Collaborator

(none)

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Maintaining the normal function of the pulmonary microvascular barrier is critical for ARDS treatment. To assess the relationship between the HAS2 protein level, HA content and the clinical prognosis of ARDS in patients with ARDS. Compare the HAS2 protein levels, HMW-HA and LMW-HA levels, endothelial injury indicators, and lungs in the blood of severe and non-ARDS severe patients and healthy adults admitted to the ICU. The correlation between permeability, disease severity and prognosis to explore the predictability of HAS2-HA on the clinical outcome of ARDS.

Condition or Disease	Intervention/Treatment	Phase
Hyaluronic Acid

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

60 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

The Role and Mechanism of O-GlcNAc Glycosylation Modified HAS2 in the Hyaluronic Acid Synthesis in ARDS

Anticipated Study Start Date :

Oct 1, 2021

Anticipated Primary Completion Date :

Jul 31, 2022

Anticipated Study Completion Date :

Sep 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
ARDS group 1.85 years≥Age≥18 years. 2.Moderate-to-severe ARDS, defined by the ARDS Definition Task Force in the Berlin definition (partial pressure of arterial oxygen [PaO2]:FiO2 ratio ≤200 mmHg with a PEEP ≥5 cmH2O). 3.Diagnosis of ARDS less than 72 hours. 4.Just observation
Critically ill patients without ARDS group Unstable vital signs, rapid changes in the condition, unstable function of more than two organ systems (excluding the respiratory system), decline or failure, the development of the disease may endanger the life of the patient.
healthy adult group Healthy adults, voluntarily join the study.

Outcome Measures

Primary Outcome Measures

28-day fatality Rate [28 days after enrollment]
28-day mortality (patients will be followed for 28 days)
90-day fatality rate [90 days after enrollment]
90-day mortality (patients will be followed for 90 days)
ICU hospital stay [through study completion, an average of 4 week]
Length of ICU stay
ICU fatality rate [through study completion, an average of 4 week]
The ratio of the total number of deaths from all causes of the enrolled patients during ICU hospitalization.
Wearing time from mechanical ventilation [through study completion，an average of 4 week]
successful weaning defined as the absence of the requirement for ventilatory support, without reintubation
Peripheral blood HMW-HA and LMW-HA levels [0, 1, 3, 7 days after enrollment]
ELISA method to separate and detect HMW-HA and LMW-HA levels（Units of Measure unit nM/ml）
HAS2 protein content in peripheral blood [0, 1, 3, 7 days after enrollment]
ELISA method detects HAS2 protein in peripheral blood

Secondary Outcome Measures

ENOS, ET-1, vWF levels in peripheral blood [0, 1, 3, 7 days after enrollment]
ELISA method to detect eNOS, ET-1, vWF in peripheral blood to evaluate endothelial cell damage（Measure unit ng/ml）
Levels of bound mucinoglycans-1, nitric oxide, and acetylheparin sulfate in peripheral blood [0, 1, 3, 7 days after enrollment]
glycocalyx levels of the endothelium were assessed by measuring the levels of mucin polysaccharide-1, nitric oxide and acetyl heparan sulfate in peripheral blood by ELISA assay（Measure unit ng/ml）
In peripheral blood, IL-1α, IL-6, neutrophils, lymphocytes, descending Procalcin, C-reactive protein value [0, 1, 3, 7 days after enrollment]
The ELISA method detects IL-1α and IL-6 in the blood, and records the blood neutrophils, lymphocytes, and vary in procalcin and C-reactive protein to assess the inflammatory response of ARDS(Measure unit pg/ml）

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

1.85 years≥Age≥18 years. 2.Moderate-to-severe ARDS, defined by the ARDS Definition Task Force in the Berlin definition (partial pressure of arterial oxygen [PaO2]:FiO2 ratio ≤200 mmHg with a PEEP ≥5 cmH2O).

3.Diagnosis of ARDS less than 72 hours.

Exclusion Criteria:

All patients who meet any of the following criteria will be excluded at enrollment and randomization.

Severe chronic respiratory diseases requiring long-term home oxygen therapy or noninvasive MV.
Undrained pneumothorax or subcutaneous emphysema.
Severe neuromuscular disease.
Hemodynamic instability (>30% increase in vasopressors within 6 hours or norepinephrine >0.5 ug/kg/min) (Am J Respir Crit Care Med. 2020; 201(2):178-187) .
Contraindications to hypercapnia, such as intracranial hypertension or acute coronary syndrome.
Severe other organs dysfunction with a low expected survival (7 days) or palliative care.
Solid organ or hematologic tumors with the expected survival time less than 30 days.
Participating in other clinical trials within 30 days.
Pregnancy.
Refusal to sign the informed consent.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Southeast University, China

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Ling Liu, professor, Southeast University, China

ClinicalTrials.gov Identifier:

NCT05055557

Other Study ID Numbers:

ZDHMWHA

First Posted:

Sep 24, 2021

Last Update Posted:

Sep 24, 2021

Last Verified:

Sep 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Ling Liu, professor, Southeast University, China

Acute respiratory distress syndrome

Pulmonary microvascular endothelial barrier;

Hyaluronic acid

Hyaluronic acid synthase 2

Study Results

No Results Posted as of Sep 24, 2021