The Role of Circulating CircRNAs and MicroRNAs in Acute Lung Injury (TRCCMALI)

Relationship Between Circulating CircRNAs and MicroRNAs and Severity of Experimental and Clinical ALI/ARDS

Efforts to identify circulating factors that predict severity of acute lung injury/acute respiratory distress syndrome（ALI/ARDS）patients is unrevealing. The primary purpose of this study is to verify circRNAs and microRNAs might be potential novel ALI/ARDS biomarkers and could play roles in pathogenesis of ALI/ARDS.

Study Overview

• Status: Recruiting
• Conditions: Acute Respiratory Distress Syndrome; Acute Lung Injury

Detailed Description

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a devastating cause of morbidity and mortality characterized by alveolar epithelial and endothelial injury. Despite recent advances in pathogenetic mechanisms and therapy strategies of ALI, efforts to identify circulating factors that predict severity of ALI/ARDS patients have been unrevealing.

Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNA with a covalently continuous closed-loop structure. Compared with traditional linear RNAs, circRNAs are more stable and resistant to RNase R due to the absence of 5' caps and 3' tails, which show clear advantages in acting as novel molecular biomarkers for many diseases. In addition, many studies have reported that circRNAs can bind to microRNAs (miRNAs), acting as "miRNA sponges" which are named competitive endogenous RNAs (ceRNAs), and can regulate gene expression at the transcriptional or post-transcriptional level. Evidence indicates that circRNAs play important roles in cancers and other diseases such as tuberculosis and intervertebral disc degeneration. As no published research has studied the expression and role of circRNAs in the pathology and pathogenesis of ALI/ARDS, the investigators aimed to validate the aberrant expression of circRNAs in ALI/ARDS and explore the potential pathological mechanism in which circRNAs are involved.

• Study Type: Observational
• Enrollment (Anticipated): 250

Contacts and Locations

• Study Contact: Name: Zhao-fan Xia, MD;PHD; Phone Number: 86-21-31161821; Email: xiazhaofan@163.com
• Study Contact Backup: Name: Yong Jiang, MD; Phone Number: 86-15721570244; Email: jiangyong233@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Recruiting
      • Department of Burn and Trauma Sugery, Changhai Hospital
      • Contact: Yong Jiang, MD; Phone Number: 86-15721570244; Email: jiangyong233@163.com
      • Contact: Zhao-fan Xia, MD;PHD; Phone Number: +862131161821; Email: xiazhaofan@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with and without ARDS were screened from Changhai Hospital. Patients were enrolled consecutively over a 2-year time period (2017-2018). All enrolled patients with ALI met the American-European Consensus Committee criteria.In addition, healthy individuals were recruited from the general population.

Description

Inclusion Criteria:

• Clinical diagnosis of ALI/ARDS
• Informed consent was obtained from either the subjects themselves or from designated surrogates before enrollment in the study.

Exclusion Criteria:

• Patients who have chronic lung disease before enrollment.
• Patients who have severe organ dysfunction, autoimmune diseases and tumor.
• Women who are pregnant or breast-feeding.
• Patients who, in the opinion of the Investigator, have any other medical condition which renders the patient unable to complete the study or which would interfere with optimal participation in the study or produce significant risk to the patient.
• Patients participating in or planning to enroll in another clinical trial during the time of the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
ARDS patients; 137 patients were enrolled consecutively over a two-year time period (2017-2018) and identified as ARDS prospectively according to the Berlin definitions of the European Society of Intensive Care Medicine and American Thoracic Society on ARDS. Exclusion criteria were an age of less than 18 years, pregnancy, chronic obstructive pulmonary disease according to medical history and failure to obtain informed consent.
Healthy volunteers; Forty healthy volunteers recruited from the general population who had no significant medical history and no medications were categorized as control patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Receiving Mechanical Ventilation		up to 28 days
Fraction of Inspired Oxygen (FiO2)/Partial Arterial Oxygen Pressure (PO2)		up to 28 days
Acute Physiology and Chronic Health Evaluation (APACHE) II Scores	APACHE II scores range from 0 to 71. A higher values represent a worse outcome	up to 28 days
plasma circRNAs		Day 3
plasma microRNAs		Day 3

Secondary Outcome Measures

Outcome Measure	Time Frame
Length of Stay in the ICU	1 year
Length of Hospital Stay	1 year
Days of Unassisted Ventilation	1 year
Death	up to 28

Collaborators and Investigators

• Sponsor: Changhai Hospital
• Investigators: Study Director: Zhao-fan Xia, MD;PHD, Department of Burn Sugery, Changhai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: December 4, 2018
• First Submitted That Met QC Criteria: December 5, 2018
• First Posted (Actual): December 6, 2018

Study Record Updates

• Last Update Posted (Actual): December 6, 2018
• Last Update Submitted That Met QC Criteria: December 5, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: microRNAs; circRNAs
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Wounds and Injuries; Infant, Newborn, Diseases; Infant, Premature, Diseases; Thoracic Injuries; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: 20181204

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