Clinical trial NCT06917547: Study on PAD and CAS Based on Omics and Imaging
Official title: Study on the Pathogenesis of PAD and CAS Based on Multi-omics Analysis and Multi-modal Imaging Technology
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Peripheral Artery Disease
Carotid Artery Stenosis
Artery Stenosis
Keywords: Peripheral artery disease
Carotid Artery Stenosis
NIR-II Imaging
V-flow Imaging
Laser Speckle Imaging
Single-cell transcriptomics
Proteomics
Lipidomics
Metabolomics
Lead sponsor: Second Hospital of Shanxi Medical University
Sponsor class: OTHER
First posted: 2025-04-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population will consist of patients diagnosed with Peripheral Artery Disease (PAD) or Carotid Artery Stenosis (CAS) who are admitted to the Department of Vascular Surgery at the Second Hospital of Shanxi Medical University. Eligible participants will be males or females aged between 18 and 85 years. Patients must be conscious, fully informed about the study, and willing to provide written informed consent. The study aims to enroll a diverse cohort to ensure representative findings. Exclusion criteria include non-atherosclerotic stenosis, prior interventional or surgical treatments for PAD, significant cardiac, hepatic, or renal dysfunction, acute infections, and other conditions that may confound the study results. Pregnant or breastfeeding women and individuals who have participated in other clinical trials within the past 3 months will also be excluded.

Brief summary: This study aims to investigate the pathogenesis of Peripheral Artery Disease (PAD) and Carotid Artery Stenosis (CAS) using a comprehensive multi-omics and multi-modal imaging approach. The study will enroll patients diagnosed with PAD or CAS and perform advanced imaging techniques, including NIR-II Imaging, DUS-based V-flow Imaging, and Laser Speckle Imaging, to assess vascular structure and function. Simultaneously, single-cell transcriptomics, metabolomics, lipidomics, and proteomics analyses will be conducted on patient samples to identify key molecular targets and pathways involved in disease progression. Machine learning algorithms will be employed to integrate imaging and multi-omics data, enabling the development of predictive models for more accurate disease diagnosis and stratification. The findings from this study are expected to provide novel insights into the molecular mechanisms underlying PAD and CAS and contribute to the development of personalized therapeutic strategies.

Detailed description: Background and Rationale Peripheral Artery Disease (PAD) and Carotid Artery Stenosis (CAS) are prevalent vascular disorders associated with significant morbidity and mortality. Despite advances in diagnostic and therapeutic approaches, the molecular mechanisms driving these diseases remain poorly understood. This study leverages cutting-edge multi-omics technologies and advanced imaging modalities to unravel the complex pathogenesis of PAD and CAS, with the ultimate goal of identifying novel biomarkers and therapeutic targets.

Study Objectives Primary Objective: To integrate multi-modal imaging data (NIR-II Imaging, DUS-based V-flow Imaging, and Laser Speckle Imaging) with multi-omics data using machine learning algorithms for improved disease prediction and stratification.

Study Design

This is a prospective, observational study involving patients diagnosed with PAD or CAS. The study will include the following components:

Imaging Analysis:

1. NIR-II Imaging: To visualize deep tissue vascular structures and hemodynamics.
2. DUS-based V-flow Imaging: To assess blood flow dynamics and vascular stenosis.
3. Laser Speckle Imaging: To evaluate microvascular perfusion and endothelial function.

Multi-Omics Analysis:

1. Single-cell Transcriptomics: To profile gene expression at the single-cell level and identify cell-type-specific changes.
2. Metabolomics and Lipidomics: To characterize metabolic and lipid profiles associated with disease progression.
3. Proteomics: To identify differentially expressed proteins and signaling pathways.
4. Data Integration and Machine Learning:

Imaging and multi-omics data will be integrated using advanced machine learning algorithms to develop predictive models for disease diagnosis, progression, and therapeutic response.

Study Population The study will enroll patients diagnosed with PAD or CAS, along with age- and sex-matched healthy controls. Inclusion and exclusion criteria will be applied to ensure a homogeneous study population.

Expected Outcomes

1. Identification of key molecular and cellular pathways involved in PAD and CAS pathogenesis.
2. Development of a multi-modal predictive model for accurate disease diagnosis and stratification.
3. Discovery of novel biomarkers and therapeutic targets for personalized medicine.

Ethical Considerations The study protocol has been reviewed and approved by the Institutional Review Board (IRB) to ensure the protection of human subjects. Informed consent will be obtained from all participants prior to their enrollment in the study.

Significance This study represents a pioneering effort to integrate multi-omics and multi-modal imaging data for a comprehensive understanding of PAD and CAS. The findings are expected to advance the field of vascular biology and contribute to the development of precision medicine approaches for these debilitating diseases.

Eligibility criteria: Inclusion Criteria:

1. The study subjects are inpatients from the Department of Vascular Surgery at the Second Hospital of Shanxi Medical University.
2. Males or females aged between 18 and 85 years.
3. Diagnosed with Peripheral Artery Disease (PAD) or Carotid Artery Stenosis (CAS).
4. Participants are conscious, fully informed about the study content, and have signed the informed consent form, agreeing to participate in this study.

Exclusion Criteria:

1. Non-atherosclerotic stenosis (e.g., vasculitis or dissection).
2. PAD patients who have previously undergone interventional treatments (e.g., balloon angioplasty or stent placement) and/or surgical procedures.
3. Patients with heart failure classified as NYHA Class II-IV or those with a history of coronary artery disease.
4. Patients with acute infections, tumors, severe arrhythmias, psychiatric disorders, or drug/alcohol addiction.
5. Significant liver dysfunction or a history of liver diseases, including: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding twice the upper limit of normal. History of cirrhosis, hepatic encephalopathy, esophageal varices, or portosystemic shunt.
6. Significant renal dysfunction or a history of kidney diseases, including: Serum creatinine levels exceeding 1.5 times the upper limit of normal. History of dialysis or nephrotic syndrome.
7. Pregnant women, those planning to become pregnant, or breastfeeding women.
8. Participation in other clinical trials within the past 3 months.
9. Refusal to sign the informed consent form or participate in this study.

Primary outcomes:
measure: Time related NIR-II parameters for CAS and PAD patients
timeFrame: Baseline, 6 months
measure: Intensity related NIR-II parameters for CAS and PAD patients
timeFrame: Baseline, 6 months
measure: Time-intensity related NIR-II parameters for CAS and PAD patients
timeFrame: Baseline, 6 months
measure: Assessment of Wall Shear Stress (WSS) Using V-flow Imaging
timeFrame: Baseline, 6 months
measure: Assessment of Microvascular Perfusion in the Dorsum of the Foot Using Laser Speckle Imaging in Patients with PAD and CAS
timeFrame: Baseline, 6 months
measure: Single-cell Transcriptomics for CAS and PAD patients
timeFrame: Baseline, 6 months
measure: Proteomics for CAS and PAD patients
timeFrame: Baseline, 6 months
measure: Lipidomics for CAS and PAD patients
timeFrame: Baseline, 6 months
measure: Metabolomics for CAS and PAD patients
timeFrame: Baseline, 6 months
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Second Hospital of Shanxi Medical University
name: Honglin Dong
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Hospital of Shanxi Medical University
name: Ruijing Zhang
role: STUDY_DIRECTOR
References:
citation: Ning Y, Hu J, Zhu Y, Tang W, Yan S, Li H, Zhang Z, Lu C, Ren K, Shi P, Yao T, Wang Q, Zhao Y, Gao T, Zhang R, Dong H. NIR-II imaging-based detection of early changes in lower limb perfusion in type 2 diabetes patients without peripheral artery disease. Diabetes Res Clin Pract. 2025 Mar;221:112038. doi: 10.1016/j.diabres.2025.112038. Epub 2025 Feb 8.