Impact of Traditional Chinese Medicine on the Gut Microbiota-dependent Trimethylamine N-oxide (TCM-TMAO)

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

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.

Study Overview

• Status: Unknown
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Drug: Compound Panax Notoginseng Granule; Drug: Placebo Granule

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lei Wang, Ph.D & M.D; Phone Number: 86-20-81887233-32801; Email: Dr.wanglei@139.com
• Study Contact Backup: Name: Shuai Mao, M.D; Phone Number: +8613724078381; Email: maoshuaitcm@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Recruiting
      • Guangdong Provincial Hospital of Chinese Medicine
      • Contact: Lei Wang, M.D; Phone Number: 8620-81887233-32801; Email: Dr.wanglei@139.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. acute coronary syndrome (ACS), including ST segment elevate myocardial infarction(STEMI), Non-ST-segment elevation myocardial infarction(NSTEMI) and unstable angina(UA).
2. TCM syndrome: Intermingled Phlegm and Blood Stasis.
3. Aged 18 to 80 years old.
4. sign a consent form.

Exclusion Criteria:

1. Cardiogenic shock.
2. Serious heart failure (NYHA IV or LVEF < 40%).
3. With severe valvular heart disease.
4. 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.
5. With acute cerebrovascular disease or severe mental illness.
6. With active bleeding or severe hematopoietic system disease.
7. With malignant tumor or life expectancy in less than three years.
8. Pregnancy or ready to pregnant women, nursing mothers.
9. History of taking antibiotics within the past two months.
10. Participating in other clinical subjects .
11. Failure to sign a consent form.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Compound Panax Notoginseng Granule; 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; 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.
Placebo Comparator: Placebo Granule; On the basis of the standard treatment for ACS,eligible participants are randomized to receive Placebo Granule when they enroll.	Drug: Placebo Granule; Placebo granule has the same as Compound Panax Notoginseng Granule in the appearance, shape,colour,taste,frequency and duration.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Guangdong Provincial Hospital of Traditional Chinese Medicine
• Collaborators: Beijing Genomics Institute
• Investigators: Study Director: Xiaoyan Li, Master, Guangdong Provincial Hospital of Traditional Chinese Medicine

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2017
• Primary Completion (Anticipated): May 31, 2018
• Study Completion (Anticipated): August 31, 2018

Study Registration Dates

• First Submitted: June 7, 2017
• First Submitted That Met QC Criteria: June 13, 2017
• First Posted (Actual): June 14, 2017

Study Record Updates

• Last Update Posted (Actual): December 7, 2017
• Last Update Submitted That Met QC Criteria: December 5, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: percutaneous coronary intervention; acute coronary syndrome; gut microbiota; Trimethylamine N-oxide
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome
• Other Study ID Numbers: YN2015MS21

Drug and device information, study documents

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