the Gut Microbiome and Metabolomics in Chronic Lower extreMities Threatening Ischemia (MMM)

The Gut Microbiome and Metabolomics Among Chronic Lower Extremities Threatening Ischemia Patients in China - a Prospective Observational Study

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Microtia; Chronic Limb-threatening Ischemia

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 Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Beijing Tsinghua Chang Gung Hosipital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

The Chronic limb-threatening ischemia patients and health adult without history of atherosclerotic plaque, coronary heart disease or stroke, attending Tsinghua Chang Gung Hospital in Beijing.

Description

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.

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Chronic limb-threatening ischemia; 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.
health control; sex - and age-matched healthy people (without history of atherosclerotic plaque, coronary heart disease or stroke).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bacteria or metabolites associated with prolonged survival time without above-knee amputation	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.	3years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Key bacteria in CLTI	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.	up to 1 week
Key plasma metabolites in CLTI	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.	up to 1 week

Collaborators and Investigators

• Sponsor: Beijing Tsinghua Chang Gung Hospital
• Investigators: Principal Investigator: Weiwei Wu, MD, Beijing Tsinghua Chang Gung Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2021
• Primary Completion (Estimated): May 15, 2025
• Study Completion (Estimated): May 15, 2025

Study Registration Dates

• First Submitted: February 15, 2023
• First Submitted That Met QC Criteria: January 14, 2024
• First Posted (Actual): January 24, 2024

Study Record Updates

• Last Update Posted (Actual): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 14, 2024
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Disease Attributes; Congenital Abnormalities; Otorhinolaryngologic Diseases; Atherosclerosis; Ear Diseases; Peripheral Vascular Diseases; Chronic Disease; Peripheral Arterial Disease; Ischemia; Congenital Microtia; Chronic Limb-Threatening Ischemia
• Other Study ID Numbers: 21431-4-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No