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

Official title

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

Overview

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.

Interventions

• 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 tissu
• 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

Primary outcome measures

• Correlation Between Peripheral Blood RSPO3/SDC-1 Pathway Activity and Alveolar Epithelial Injury Marker Levels [Time frame: Baseline (within 24 hours of ARDS diagnosis)]

Secondary outcome measures (1)

• Effect of RSPO3/SDC-1 Pathway Modulation on Alveolar Organoid Repair Capacity [Time frame: Within 14 days of organoid establishment]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Other

Study locations

China · 1 center

• Shanghai Xinhua hospital — Shanghai

Identifiers

NCT: NCT07129330 · XHEC-C-2025-167-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗