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

NCT07129330 | Not Yet Recruiting

• 1 other identifier: XHEC-C-2025-167-1
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Respiratory Distress Syndrome (ARDS); Age-related Impaired Alveolar Epithelial Repair

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Effect of RSPO3/SDC-1 Pathway Modulation on Alveolar Organoid Repair Capacity

  Within 14 days of organoid establishment

Other Outcomes (1)

• Diagnostic Performance of the RSPO3/SDC-1-Based Integrated Platform

  Upon completion of all sample processing (estimated by study end)

Study Arms (4)

ARDS

Procedure: Blood and Saliva

NON_ARDS

Procedure: Blood and Saliva

AGED

Procedure: RSPO3/SDC-1 pathway profiling assay

YOUNG

Procedure: RSPO3/SDC-1 pathway profiling assay

Interventions

RSPO3/SDC-1 pathway profiling assay PROCEDURE

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

AGED; YOUNG

Blood and Saliva PROCEDURE

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

ARDS; NON_ARDS

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Shanghai Xinhua hospital

Shanghai, China

Location

MeSH Terms

Conditions

Respiratory Distress Syndrome

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Jiang

CONTACT

+86 13817719616; jianglaimz@sina.com

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: 021-25077820

Study Record Dates

• First Submitted: August 12, 2025
• First Posted: August 19, 2025
• Study Start: September 1, 2025
• Primary Completion: September 1, 2025
• Study Completion (Estimated): December 30, 2029
• Last Updated: August 19, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)