the Gut Microbiome and Metabolomics in Chronic Lower extreMities Threatening Ischemia

• Conditions: Chronic Limb-threatening Ischemia; Microtia

• Registration Number: NCT06220994
• Lead Sponsor: Beijing Tsinghua Chang Gung Hospital

Brief Summary

Intestinal floras and their metabolites are involved in progressing metabolic and cardiovascular diseases. However, currently, articles related to the relationship between intestinal floras and atherosclerosis mainly focus on coronary atherosclerotic disease (CAD) population, or atherosclerosis model animals such as ApoE-/-, LDLR-/- high-fat diet mice, and there are few studies on Chronic limb-threatening ischemia (CLTI). CLTI and CAD have a similar pathological basis of atherosclerosis. It is unclear whether intestinal flora plays an essential role in the occurrence and development of CLTI. This project aims to explore the relation between microorganisms, metabolites, and CLTI.

Detailed Description

This project aims to study the intestinal flora and its metabolites in patients with CLTI, explore whether CLTI patients and CAD patients have their own characteristic flora, analyze the microorganisms and metabolites markers of poor prognosis in patients with CLTI, and screen out the key differential bacteria and metabolites that inhibit the progress of CLTI, in order to provide new insights and research basis for the treatment of CLTI.

Study Timeline

• Study Start: 2021-11-15
• Study First Submitted: 2023-02-15
• Status Verified: 2023-03
• Study First Submitted QC: 2024-01-14
• Last Update Submitted: 2024-01-14
• Study First Posted: 2024-01-24
• Last Update Posted: 2024-01-24
• Primary Completion: 2025-05-15
• Study Completion: 2025-05-15

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

Control group: sex - and age-matched healthy people (without history of atherosclerotic plaque, coronary heart disease or stroke).

Case group: resting pain for at least 2 weeks with at least one hemodynamic index: ABI<0.4,AP<50mmHg, TP or TCPO2<30mmHg. Tissue defects (ulceration or gangrene) persisted for at least 2 weeks with at least one significant PAD objective evidence: ABI<0.8, AP<100mmHg, TP or TCPO2<60mmHg.

Read More

Exclusion Criteria

1. Patients with inflammatory bowel disease, autoimmune diseases, malignancies, infectious diseases, and severe liver and kidney dysfunction (cirrhosis, CKD stage 4 and 5).
2. Patients with thromboembolic angiitis, arterial embolism, and takayasu.
3. Patients who have used probiotics or antibiotics in the last 2 months.
4. After interventional surgery and amputation below the knee or above knee.

Read More

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Bacteria or metabolites associated with prolonged survival time without above-knee amputation	3years.	The relationship between the prognosis and gut microbiota or plasma metabolomics was analyzed. Spearman correlations between CAGs, serum metabolite modules and clinical parameters were calculated using R, and both differential abundances of CAGs and CLTI-associated metabotypes were tested by the Wilcoxon rank sum test.

Secondary Outcome Measures

Name	Time	Method
Key plasma metabolites in CLTI	up to 1 week	Differential metabolites enriched in healthy group but absent in CLTI patients were explored by non-targeted metabolomics analysis of the gut contents. It includes sample grouping data analysis, metabolites annotation, and screening of differential metabolites.
Key bacteria in CLTI	up to 1 week	Differential bacteria enriched in healthy group but absent in CLTI patients were explored by metagenomic analysis of the gut microbiota. It includes species composition and abundance analysis, beta diversity, differences between groups, and RDA/CCA.

Trial Locations

Locations (1)

Beijing Tsinghua Chang Gung Hosipital; 🇨🇳 Beijing, Beijing, China