RSPO3/SDC-1 Pathway Dysfunction in Alveolar Repair After ARDS in Older Adults

Role and Mechanisms of RSPO3/SDC-1 Pathway Dysregulation in Impaired Alveolar Epithelial Repair Post-ARDS in Older Adults

Acute respiratory distress syndrome (ARDS) is a serious lung condition in which fluid builds up in the air sacs, making it hard to breathe and often requiring intensive care. Older adults fare worse because their lung-lining cells lose the ability to heal properly after injury This study will explore two key molecules-RSPO3 and Syndecan-1 (SDC-1)-that normally help alveolar (air-sac) cells regenerate. We will collect small blood samples from ARDS patients and, when patients undergo elective lung surgery, tiny pieces of healthy lung tissue. In the lab, we will also grow three-dimensional "lung organoids" from these samples to see how boosting or blocking RSPO3/SDC-1 affects cell repair

Our goals are to:

Measure RSPO3/SDC-1 activity alongside inflammatory markers (e.g., IL-6, TNF-α) to understand their roles in age-related repair failure.

Build an integrated platform for early diagnosis, disease monitoring, and treatment evaluation in older ARDS patients.

Identify molecular targets that could lead to new therapies, helping older adults recover lung function more effectively.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Respiratory Distress Syndrome (ARDS); Age-related Impaired Alveolar Epithelial Repair
• Intervention / Treatment: Procedure: Blood and Saliva; Procedure: RSPO3/SDC-1 pathway profiling assay

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Jiang; Phone Number: +86 13817719616; Email: jianglaimz@sina.com

Study Locations

• China
  • Shanghai, China
    • Shanghai Xinhua hospital
    • Contact: Jiang; Phone Number: +86 13817719616; Email: jianglaimz@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

ARDS Group: 500 adult patients with acute respiratory distress syndrome, enrolled across five age brackets (20-30, 30-40, 50-60, 70-80, and > 80 years), with 100 participants per stratum Lung Resection Control Group: 500 patients undergoing elective lobectomy for non-infectious pulmonary conditions (e.g., lung tumors, interstitial lung disease), matched by age bracket and size to the ARDS cohort

Description

Inclusion Criteria:

Clinical diagnosis of acute respiratory distress syndrome (ARDS) according to the Berlin Definition Age ≥ 65 years at enrollment First diagnosis of ARDS made within 24 hours prior to study entry Receiving either spontaneous (non-invasive) breathing support or invasive mechanical ventilation

Exclusion Criteria:

Coexisting severe cardiac, hepatic or renal failure (NYHA Class III-IV) Active pulmonary infection (e.g. pneumonia or lung abscess) Significant coagulation disorders Receipt of any cytokine-based therapy within the past 3 months Participation in another interventional clinical study within the past 3 months

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ARDS	Procedure: Blood and Saliva; Peripheral Blood: 5 mL collected into EDTA tubes; PBMCs isolated within 2 h for RT-qPCR analysis of RSPO3/SDC-1 mRNA and sandwich ELISA quantification of protein levels. Saliva: 2-3 mL unstimulated saliva naturally expectorated into sterile tubes, kept at 4 °C and processed within 2 h (centrifuged, aliquoted) before -80 °C storage
NON_ARDS	Procedure: Blood and Saliva; Peripheral Blood: 5 mL collected into EDTA tubes; PBMCs isolated within 2 h for RT-qPCR analysis of RSPO3/SDC-1 mRNA and sandwich ELISA quantification of protein levels. Saliva: 2-3 mL unstimulated saliva naturally expectorated into sterile tubes, kept at 4 °C and processed within 2 h (centrifuged, aliquoted) before -80 °C storage
AGED	Procedure: RSPO3/SDC-1 pathway profiling assay; Peripheral Blood: 5 mL collected into EDTA tubes; PBMCs isolated within 2 h for RT-qPCR analysis of RSPO3/SDC-1 mRNA and sandwich ELISA quantification of protein levels. Saliva: 2-3 mL unstimulated saliva naturally expectorated into sterile tubes, kept at 4 °C and processed within 2 h (centrifuged, aliquoted) before -80 °C storage Subcutaneous Fat: 100-200 mg obtained during elective procedures, preserved in RNAlater at 4 °C for 24 h, then frozen at -80 °C 3D Alveolar Organoid Assay: Lung tissue-derived organoids are cultured in Matrigel and treated ex vivo with recombinant RSPO3 or SDC-1 neutralizing antibody; epithelial repair is assessed over 7 days by Ki-67 immunostaining and wound-closure measurement
YOUNG	Procedure: RSPO3/SDC-1 pathway profiling assay; Peripheral Blood: 5 mL collected into EDTA tubes; PBMCs isolated within 2 h for RT-qPCR analysis of RSPO3/SDC-1 mRNA and sandwich ELISA quantification of protein levels. Saliva: 2-3 mL unstimulated saliva naturally expectorated into sterile tubes, kept at 4 °C and processed within 2 h (centrifuged, aliquoted) before -80 °C storage Subcutaneous Fat: 100-200 mg obtained during elective procedures, preserved in RNAlater at 4 °C for 24 h, then frozen at -80 °C 3D Alveolar Organoid Assay: Lung tissue-derived organoids are cultured in Matrigel and treated ex vivo with recombinant RSPO3 or SDC-1 neutralizing antibody; epithelial repair is assessed over 7 days by Ki-67 immunostaining and wound-closure measurement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation Between Peripheral Blood RSPO3/SDC-1 Pathway Activity and Alveolar Epithelial Injury Marker Levels	Quantify RSPO3 and Syndecan-1 expression in peripheral blood (by RT-qPCR and ELISA) and measure alveolar injury biomarkers (SP-A, SP-D) in serum. Calculate Pearson or Spearman correlation coefficients between RSPO3/SDC-1 levels and SP-A/SP-D concentrations in elderly ARDS patients at baseline.	Baseline (within 24 hours of ARDS diagnosis)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of RSPO3/SDC-1 Pathway Modulation on Alveolar Organoid Repair Capacity	Assess lung organoid epithelial repair by measuring (1) percentage of Ki-67-positive cells and (2) wound-closure area in 3D alveolar organoid cultures treated with recombinant RSPO3 protein or SDC-1 neutralizing antibody versus untreated controls.	Within 14 days of organoid establishment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic Performance of the RSPO3/SDC-1-Based Integrated Platform	Evaluate the multi-marker platform combining RSPO3/SDC-1 activity and inflammatory cytokines (IL-6, TNF-α) by calculating AUC, sensitivity, specificity, PPV, and NPV for predicting impaired alveolar repair in elderly ARDS patients.	Upon completion of all sample processing (estimated by study end)

Collaborators and Investigators

• Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2025
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: August 12, 2025
• First Submitted That Met QC Criteria: August 12, 2025
• First Posted (Actual): August 19, 2025

Study Record Updates

• Last Update Posted (Actual): August 19, 2025
• Last Update Submitted That Met QC Criteria: August 12, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: XHEC-C-2025-167-1

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