REST4-AAA Registry

NCT ID: NCT07056491

Last Updated: 2025-07-09

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 70 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-07-01
• Study Completion Date: 2031-07-01

Brief Summary

This prospective observational study aims to investigate whether serum REST4 concentration can serve as a quantitative indicator correlated with abdominal aortic aneurysm (AAA) diameter and a predictive biomarker for AAA progression and rupture risk. Emerging evidence suggests that REST4, a splice variant of the RE-1 Silencing Transcription Factor (REST), is upregulated in vascular smooth muscle cells during AAA pathogenesis and may be released into circulation via exosomes. The study will enroll patients with asymptomatic AAA (diameter between 39-49 mm) and measure baseline serum REST4 levels, analyzing their association with morphological severity (maximum aortic diameter) and clinical outcomes (aneurysm growth rate, rupture and related mortality) through a 5-year follow-up period.

Detailed Description

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease characterized by progressive dilation of the abdominal aorta, ultimately leading to catastrophic rupture with high mortality. Currently, clinical management relies mainly on aneurysm diameter for risk assessment, lacking reliable biomarkers to predict disease progression or rupture risk. Emerging evidence highlights the critical role of vascular smooth muscle cell (VSMC) phenotypic switching in AAA pathogenesis. Preliminary research has identified that RE-1 Silencing Transcription Factor (REST) in VSMC undergoes alternative splicing in AAA tissues, resulting in predominant expression of its splice variant REST4 and downregulation of full-length REST. This molecular shift triggers STAT1 activation, promoting synthetic VSMC transformation.

The study hypothesizes that synthetic VSMC in AAA lesions secrete REST4 into circulation via exosomes, making serum REST4 a potential dual-parameter biomarker that quantitatively correlates with aneurysm diameter (morphological severity) and predicts disease progression and rupture risk.

This prospective observational study will systematically evaluate asymptomatic AAA patients (39-49 mm diameter) to first determine the relationship between serum REST4 levels and maximum aortic diameter. Subsequently, through 5-year follow-up, the investigators will assess the prognostic capacity of serum REST4 concentration for predicting annual aneurysm growth rates, rupture incidence, and aneurysm-specific mortality.

Validation of correlation between serum REST4 concentration and AAA progression could transform current AAA surveillance approaches by integrating molecular profiling with traditional anatomical monitoring, enabling more precise risk stratification and personalized clinical management to ultimately improve patient outcomes.

Conditions

Abdominal Aortic Aneurysm

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

mRNA level of REST4 in serum;

1. mRNA level of REST4 in serum The mRNA expression level of REST4 was measured in serum-derived exosomes using RT-qPCR at the time of patient enrollment.

2. Computed tomography angiography (CTA) Baseline maximum internal diameter of the abdominal aortic aneurysm (AAA) was determined by CTA at enrollment. During follow-up, CTA was performed to assess the increase in maximum AAA diameter.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Presence of an infrarenal AAA with a maximum diameter of 39-49 mm;

2. Han nationality;

3. Between 50 years or more, no gender limit;

4. No mental illness;

5. Subjects voluntarily participate in this study, sign an informed consent form, have good compliance, and cooperate with follow-up.

Exclusion Criteria

1. Previous infrarenal aortic surgery;

2. Planned major surgery;

3. Known aortic dissection;

4. Have received any other clinical trial treatment within 1 year;

5. Systemic treatment with corticosteroids or other systemic immunomodulatory therapy;

6. Severe infections, including but not limited to infections requiring hospitalization, bacteremia, severe pneumonia, etc.;

7. Known or suspected inherited connective tissue disorder;

8. Known or suspected prostate cancer;

9. Calculated creatinine clearance of less than 30 ml/min;

10. Known significant liver disease;

11. Known human immunodeficiency virus infection at the time of screening；

12. Serious concomitant illness associated with life expectancy of less than 2 years；

13. Any other significant and unstable condition that could limit compliance with the trial protocol.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RenJi Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Ren Ji Hospital Afflited to School of Medicine, Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, China

Countries

China

Central Contacts

Jun Pu, MD,PhD

Role: CONTACT

pujun310@hotmail.com

86-21-68383477

Yinan Li, MD,PhD

Role: CONTACT

liyinan0402@126.com

86-21-68383477

Facility Contacts

Jun Pu, MD,PhD

Role: primary

pujun310@hotmail.com

86-21-68383477

Other Identifiers

REST4-AAA

Identifier Type: -

Identifier Source: org_study_id