Gut Microbiota Modulation With Synbiotics as Secondary Prevention After Acute Coronary Syndrome: A Randomized-Controlled Trial Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 80
- 主要终点
- TMAO
研究概览
简要总结
Acute coronary syndrome (ACS) remains one of the leading causes of morbidity and mortality worldwide despite major advances in acute management and secondary prevention. Gut dysbiosis has been described as linked to cardiovascular events. Modulating the gut microbiota through symbiotics-a combination of probiotics and prebiotics-represents a promising, low-risk and widely accessible strategy to influence these pathways and contribute to the enhancement of cardiovascular prevention, with regards to the global burden as well as health costs.
The SYMBIO-ACS study is therefore designed to assess the effects of a symbiotic intervention on TMAO levels and identify new cardiometabolic biomarkers in patients following ACS, providing essential pilot data for future larger-scale preventive trials.
详细描述
Modulating the gut microbiota through symbiotics-a combination of probiotics and prebiotics-represents a promising, low-risk and widely accessible strategy to influence these pathways and contribute to the enhancement of cardiovascular prevention, with regards to the global burden as well as health costs. Symbiotics may reduce TMAO levels, decrease systemic inflammation, and support metabolic regulation. However, evidence in post-ACS patients remains limited, and controlled clinical trials addressing mechanistic biomarkers are needed. The SYMBIO-ACS study is therefore designed to assess the effects of a symbiotic intervention on TMAO levels and identify new cardiometabolic biomarkers in patients following ACS, providing essential pilot data for future larger-scale preventive trials.
The aim of the study is to detect a 50% TMAO reduction (and a difference of 1 to 2 μmol/L) with gut modulation with symbiotics after acute coronary syndrome, and identify other relevant anthropometric and biomarkers Design: Prospective monocentric randomized-control trial with superiority design.
Population: Outpatient cardiology clinic or emergency department of the hospital of Biel in Switzerland.
Protocol:
Patients diagnosed with an ACS (less than one week ago) will be identified by doctors of the cardiology department of the Biel Spital Zentrum (Switzerland) both in the ambulatory consultation and emergency department, where cardiologist act as consultants. They will be informed on the study and if wished be given a 48 hours reflection before agreeing with the consent form. All patients, regardless of our study, will be offered the best-guideline directed medical therapy (according to either performed PCI or conservative treatment) with implantation of lifestyle measures (advice with brochure on the Mediterranean diet, physical activity, and tobacco cessation). Then, they will be randomized 1:1 with a software (stratification for age, sex, vegetarian diet and cardiovascular risk factors (cardiovascular risk factors (hypertension, mellitus diabetes, dyslipidemia)) to receive a 10 week daily symbiotic supplementation or the standard therapy alone (no placebo).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed Consent as documented by signature
- •Adult patients capable of providing discernment informed consent
- •Recent (< 1 week) diagnosis of acute coronary syndrome as defined in the last 2023 ESC guidelines and the Fourth universal definition of myocardial infarction, including unstable angina or myocardial infarction with or without ST-elevation, managed either with best guideline-directed medical therapy or percutaneous coronary intervention.
- •Myocardial injury: Elevated cardiac troponins (cTn) value above the 99th percentile URL. The injury is considered acute if there is a rise and/or fall of cTn values.
- •Unstable angina: Myocardial ischaemia at rest or on minimal exertion in the absence of acute cardiomyocyte injury/necrosis. Prolonged (>20 min) angina at rest; new onset of severe angina; angina that is increasing in frequency, longer in duration, or lower in threshold; or angina that occurs after a recent episode of MI
- •Type 1 myocardial infarction: Detection of a rise and/or fall of cTn values with at least one value above the 99th percentile URL and with at least one of the following: Symptoms of acute myocardial ischaemia; New ischaemic ECG change; Development of pathological Q waves; Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischaemic aetiology;Identification of a coronary thrombus by angiography including intracoronary imaging or by autopsy
- •Mastering French or German or capacity to be helped with adequate translation
排除标准
- •Contraindications to symbiotics as listed in Section 3.5.5, that is: immunocompromised individuals, intensive care patients (or critical state), severe valvulopathiesvalvular heart diseases, endocarditis antecedent, known allergy, chronic intestinal diseases or risk factors for small intestine bacterial overgrowth (SIBO) (severe malabsorption or history of digestive surgery), or severe comorbidities (see under)
- •Severe hepatic or renal dysfunction (defined as eGFR <30 mL/min/1,73 m², dialysis or Child-Pugh score class C)
- •Limited life expectancy (<1 year) or progressive malignant disease
- •Type 2 myocardial infarction: Detection of a rise and/or fall of cTn values with at least one value above the 99th percentile URL, and evidence of an imbalance between myocardial oxygen supply and demand unrelated to acute coronary athero-thrombosis, requiring at least one of the following: Symptoms of acute myocardial ischaemia; New ischaemic ECG changes; Development of pathological Q waves; Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischaemic aetiology.
- •Ongoing pre/probiotic supplementation
- •Chronic antibiotherapy or within less than 3 months
- •Women who are pregnant or breast feeding
- •Intention to become pregnant during the course of the study
- •Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases (Female participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential)
- •Known or suspected non-compliance, drug or alcohol abuse, dement patients not living in assisted nurse facility care or without supervised treatment administration
- •Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
- •Previous enrolment into the current study,
- •Enrolment of the investigator, his/her family members, employees and other dependent persons
研究组 & 干预措施
Symbiotic supplementation
Supplementation with Pro-B (BioNaturis, Switzerland) for 10 weeks
干预措施: Pro-B (Bionaturis), (Dietary Supplement)
Symbiotic supplementation
Supplementation with Pro-B (BioNaturis, Switzerland) for 10 weeks
干预措施: Guideline-Directed Medical Therapy (GDMT) (Other)
Control
Standard guideline-directed medical therapy
干预措施: Guideline-Directed Medical Therapy (GDMT) (Other)
结局指标
主要结局
TMAO
时间窗: At inclusion, 10 weeks and 1 year
TMAO level
次要结局
- SCFA and bile acids profile(At inclusion, 10 weeks and 1 year)
- LPS(At inclusion, 10 weeks and 1 year)
- Lipid profile (LDL, High total/HDL-cholesterol and LDL/HDL-cholesterol)(At inclusion, 10 weeks and 1 year)
- Height(At inclusion, 10 weeks and 1 year)
- Weight(At inclusion, 10 weeks and 1 year)
- BMI(At inclusion, 10 weeks and 1 year)
- Systolic Blood pressure(At inclusion, 10 weeks and 1 year)
- hsCRP(At inclusion, 10 weeks and 1 year)
- HbA1c(At inclusion, 10 weeks and 1 year)
- Malondialdehyde(At inclusion, 10 weeks and 1 year)
- Total antioxidant capacity(At inclusion, 10 weeks and 1 year)
- Imidazole propionate(At inclusion, 10 weeks and 1 year)
- Indoxyl Sulfate(At inclusion, 10 weeks and 1 year)
- Interleukins (IL1β, IL6, IL10)(At inclusion, 10 weeks and 1 year)
- IFN-γ(At inclusion, 10 weeks and 1 year)
- TNF-α(At inclusion, 10 weeks and 1 year)
- 7-item Seattle Angina Questionnaire (SAQ-7)(At inclusion, 10 weeks and 1 year)
- Clinical questionnaire(At inclusion, 10 weeks and 1 year)
- Life's Essential 8 (LE8)(At inclusion, 10 weeks and 1 year)
研究者
Johan Schwab
Dr. MD, Clinical Lead
Centre Hospitalier de Bienne