Impact of Traditional Chinese Medicine on the Gut Microbiota-dependent Trimethylamine N-oxide

Study Overview
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Brief Summary
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Recent studies highlight the participation of gut microbes in the pathogenesis of both atherosclerotic heart disease and its adverse thrombotic events. Trimethylamine N-oxide (TMAO) is a plasma metabolite shown to be formed through a metaorganismal pathway involving nutrient precursors abundant in a Western diet and the sequential action of gut microbiota. Numerous studies reveal an association between systemic TMAO levels and cardiovascular risks in a variety of stable cohorts. The purpose of this study is to evaluate the efficacy of traditional Chinese Medicine formular (Compound pseudo-ginseng granules ) on the level of TMAO for the patient with acute coronary syndrome(ACS) undergoing percutaneous coronary intervention. 80 patients with ACS would be randomly allocated into interventional group(IG) and control group(CG). The patients in the IG would be administered by oral Compound pseudo-ginseng granules (twice per day ) for 90 days and those in the CG would receive the placebo twice per day during the same period. All of subjects would be administered with standard therapy in accordance with AHA/ACC guideline for ST-elevation myocardial infarction(STEMI) and Non ST-elevation myocardial infarction(NSTEMI).The primary endpoint is the plasma level of TMAO at 90-day follow-up. The second endpoint is the level of lipid, score of The Seattle Angina, fecal DNA extraction and pyrosequencing.

Official Title
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Impact of Traditional Chinese Medicine on the Gut Microbiota-dependent Trimethylamine N-oxide in Acute Coronary Syndromes : A Randomized Placebo Controlled Trial

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Drug: Compound Panax Notoginseng Granule
* Drug: Placebo Granule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: acute coronary syndrome (ACS), including ST segment elevate myocardial infarction(STEMI), Non-ST-segment elevation myocardial infarction(NSTEMI) and unstable angina(UA). TCM syndrome: Intermingled Phlegm and Blood Stasis. Aged 18 to 80 years old. sign a consent form. Exclusion Criteria: Cardiogenic shock. Serious heart failure (NYHA IV or LVEF < 40%). With severe valvular heart disease. Severe hepatic or renal insufficiency, with serum Alanine aminotransferase ( ALT) 3 times higher than normal ceiling or serum creatinine not lower than 265 μmol/L. With acute cerebrovascular disease or severe mental illness. With active bleeding or severe hematopoietic system disease. With malignant tumor or life expectancy in less than three years. Pregnancy or ready to pregnant women, nursing mothers. History of taking antibiotics within the past two months. Participating in other clinical subjects . Failure to sign a consent form.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Compound Panax Notoginseng Granule<br>On the basis of the standard treatment for ACS,eligible participants are randomized to receive Compound Panax Notoginseng Granule when they enroll. | Drug: Compound Panax Notoginseng Granule<br>* Dosage form:granule. Composition: Panax notoginseng,Codonopsis pilosula,Salvia miltiorrhiza,Pinellia ternata,Medicated Leaven,Coptis chinensis,Citrus reticulata Blanco,etc. Frequency:two times a day, one package per time. Duration:three months.<br>|
| Placebo Comparator: Placebo Granule<br>On the basis of the standard treatment for ACS,eligible participants are randomized to receive Placebo Granule when they enroll. | Drug: Placebo Granule<br>* Placebo granule has the same as Compound Panax Notoginseng Granule in the appearance, shape,colour,taste,frequency and duration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the plasma level of TMAO | Trimethylamine-N-Oxide(μM) is relative to the prognostic of ACS. | baseline | 
| the plasma level of TMAO | Trimethylamine-N-Oxide(μM) is relative to the prognostic of ACS. | 90-days post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| metagenomic DNA sequencing analysis of faecal microbiome | high-throughput sequencing and big data analytics | baseline | 
| metagenomic DNA sequencing analysis of faecal microbiome | high-throughput sequencing and big data analytics | 90-days post-procedure | 
| major adverse cardiac event | frequency of the reported cardiovascular events (defined as death, non fatal myocardial infarction,target vessel revascularization and stent thrombosis ) | 90-days post-procedure | 
| cardiac function | left ventricular ejection fraction(LVEF) evaluated by echo | baseline | 
| cardiac function | left ventricular ejection fraction(LVEF) evaluated by echo | 90-day at follow-up | 
| Seattle Angina Questionnaire score | The Seattle Angina Questionnaire is a valid and reliable instrument that measures five clinically important dimensions of health in patients with coronary artery disease (physical limitation, anginal stability, anginal frequency, treatment satisfaction, and disease perception). | 90-days | 
| The traditional Chinese medicine syndrome scale | The score of phlegm and of blood stasis syndromes is evaluated by Phlegm and blood stasis syndrome questionnaire. | change from baseline at 90-days | 
| lipid metabolism | low-density lipoprote in cholesterol in mmol/L | change from baseline at 90-days | 
| lipid metabolism | total cholesterol in cholesterol in mmol/L | change from baseline at 90-days | 
| inflammatory factors | C-reactive protein in mg/L | change from baseline at 90-days | 
| platelet function | maximal aggregation rate of platelet in percent | change from Baseline at 90-days | 
| cardiac biomarkers of necrosis | cardiac troponin T (cTnT) in ug/L | Change from Baseline at 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute coronary syndrome, gut microbiota, Trimethylamine N-oxide, percutaneous coronary intervention