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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hyaluronic Acid

• Study Type: Observational
• Enrollment (Anticipated): 60

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

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.

1. Severe chronic respiratory diseases requiring long-term home oxygen therapy or noninvasive MV.
2. Undrained pneumothorax or subcutaneous emphysema.
3. Severe neuromuscular disease.
4. 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) .
5. Contraindications to hypercapnia, such as intracranial hypertension or acute coronary syndrome.
6. Severe other organs dysfunction with a low expected survival (7 days) or palliative care.
7. Solid organ or hematologic tumors with the expected survival time less than 30 days.
8. Participating in other clinical trials within 30 days.
9. Pregnancy.
10. Refusal to sign the informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ENOS, ET-1, vWF levels in peripheral blood	ELISA method to detect eNOS, ET-1, vWF in peripheral blood to evaluate endothelial cell damage（Measure unit ng/ml）	0, 1, 3, 7 days after enrollment
Levels of bound mucinoglycans-1, nitric oxide, and acetylheparin sulfate in peripheral blood	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）	0, 1, 3, 7 days after enrollment
In peripheral blood, IL-1α, IL-6, neutrophils, lymphocytes, descending Procalcin, C-reactive protein value	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）	0, 1, 3, 7 days after enrollment

Collaborators and Investigators

• Sponsor: Southeast University, China

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2021
• Primary Completion (Anticipated): July 31, 2022
• Study Completion (Anticipated): September 30, 2022

Study Registration Dates

• First Submitted: September 12, 2021
• First Submitted That Met QC Criteria: September 15, 2021
• First Posted (Actual): September 24, 2021

Study Record Updates

• Last Update Posted (Actual): September 24, 2021
• Last Update Submitted That Met QC Criteria: September 15, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Acute respiratory distress syndrome; Hyaluronic acid; Pulmonary microvascular endothelial barrier;; Hyaluronic acid synthase 2
• Other Study ID Numbers: ZDHMWHA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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