Effect of Berberine for Endothelial Function and Intestinal Microflora in Patients With Coronary Artery Disease
- Conditions
- Stable Coronary Artery DiseasePercutaneous Coronary Intervention
- Interventions
- Registration Number
- NCT04434365
- Lead Sponsor
- Peking Union Medical College Hospital
- Brief Summary
The purpose of this study is to conduct a single-center, randomized, open-label, controlled, dose-escalating, parallel-group study, evaluating the effects and change of endothelial function and gut microbiota after berberine administration in patients with stable coronary artery disease who are at \> 8 but ≤ 40 weeks after elective percutaneous coronary intervention
- Detailed Description
In the present study, about 48 patients with stable coronary artery disease who are at \> 8 but ≤ 40 weeks after elective percutaneous coronary intervention. The total study duration is expected to be approximately 14 weeks per patient, including a screening period, a 12±1 week treatment period, Randomization was computer generated. After screening, eligible subjects will be randomly assigned into one of the following two groups: Berberine+therapy Arm or Standard therapy Arm. The primary objective is to determine whether a combination of berberine and coronary artery disease standard therapy is preferable to either berberine alone or standard therapy alone.
The visit schedule will be as follows:
Visit 1: Day -7 to Day -1, Screening/Enrolment; Visit 2: Day 1, Randomization/First dose; Visit 3: Week 4±1, Dose adjustment 1, BBR (100mg, tid); Visit 4: Week 8±1, Dose adjustment 2, BBR (200mg, tid); Visit 5: Week 12±1, End of Treatment (EOT) /Last dose, BBR (300mg, tid); Safety visit.
We perform cross-sectional comparisons between the two arms and longitudinal comparisons within each arm to evaluate the indicators as follows:
1. . Endothelial function, as measured by Flow mediated dilation (FMD) from baseline to 12-week follow-up;
2. . Gut microbiota, as sequenced by metagenomic sequencing from baseline to 12-week follow-up.
Blood and feces samples will be collected before and after treatment. Flow mediated dilation (FMD), HbA1C, fasting plasma glucose (FPG), lipids and cholesterol level, inflammatory factors, amino acids, bile acids and other metabolic related components and parameters will be measured. Furthermore, the change of gut microbiota will be evaluated too.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 24
Patients with stable coronary artery disease undergo elective PCI >8 weeks, but ≤40 weeks
- Planned coronary revascularization, including PCI and coronary artery bypass graft (CABG) during the study period.
- Subjects with uncontrolled high blood pressure
- Recent (within 4 weeks) dose adjustment of any standard therapy agents
- Recent (within 4 weeks) use of berberine
- History of intolerance to berberine.
- Cr>1.5mg/dL; ALT level exceeds the upper limit of 3 times
- Heart failure or LVEF <50%
- Uncontrolled arrhythmia
- Pregnancy or lactation
- Malignant tumor or life expectancy is less than half a year
- Subjects who can not complete the follow-up
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Berberine+standard therapy Arm Statin In the Berberine Arm, patients will receive berberine 100 mg twice daily for 4±1 weeks (Stage 1); then, 200 mg twice daily for 4±1 weeks (Stage 2); then, 300 mg twice daily for 4±1 weeks (Stage 3) in addition to standard treatment, including aspirin (100mg/day), clopidogrel (75mg/day), statins, the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, calcium channel blockers, beta-blockers, and/or antidiabetic therapy (including insulin or oral medication) was decided on an individual basis by the attending physician for 12±1 weeks. Berberine+standard therapy Arm Aspirin In the Berberine Arm, patients will receive berberine 100 mg twice daily for 4±1 weeks (Stage 1); then, 200 mg twice daily for 4±1 weeks (Stage 2); then, 300 mg twice daily for 4±1 weeks (Stage 3) in addition to standard treatment, including aspirin (100mg/day), clopidogrel (75mg/day), statins, the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, calcium channel blockers, beta-blockers, and/or antidiabetic therapy (including insulin or oral medication) was decided on an individual basis by the attending physician for 12±1 weeks. Standard therapy Arm Aspirin In the Control Arm, patients will receive standard treatment, including aspirin (100mg/day), clopidogrel (75mg/day), statins, the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, calcium channel blockers, beta-blockers, and/or antidiabetic therapy (including insulin or oral medication) was decided on an individual basis by the attending physician for 12±1 weeks. Standard therapy Arm Statin In the Control Arm, patients will receive standard treatment, including aspirin (100mg/day), clopidogrel (75mg/day), statins, the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, calcium channel blockers, beta-blockers, and/or antidiabetic therapy (including insulin or oral medication) was decided on an individual basis by the attending physician for 12±1 weeks. Berberine+standard therapy Arm Clopidogrel In the Berberine Arm, patients will receive berberine 100 mg twice daily for 4±1 weeks (Stage 1); then, 200 mg twice daily for 4±1 weeks (Stage 2); then, 300 mg twice daily for 4±1 weeks (Stage 3) in addition to standard treatment, including aspirin (100mg/day), clopidogrel (75mg/day), statins, the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, calcium channel blockers, beta-blockers, and/or antidiabetic therapy (including insulin or oral medication) was decided on an individual basis by the attending physician for 12±1 weeks. Standard therapy Arm Clopidogrel In the Control Arm, patients will receive standard treatment, including aspirin (100mg/day), clopidogrel (75mg/day), statins, the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, calcium channel blockers, beta-blockers, and/or antidiabetic therapy (including insulin or oral medication) was decided on an individual basis by the attending physician for 12±1 weeks. Berberine+standard therapy Arm Berberine In the Berberine Arm, patients will receive berberine 100 mg twice daily for 4±1 weeks (Stage 1); then, 200 mg twice daily for 4±1 weeks (Stage 2); then, 300 mg twice daily for 4±1 weeks (Stage 3) in addition to standard treatment, including aspirin (100mg/day), clopidogrel (75mg/day), statins, the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, calcium channel blockers, beta-blockers, and/or antidiabetic therapy (including insulin or oral medication) was decided on an individual basis by the attending physician for 12±1 weeks.
- Primary Outcome Measures
Name Time Method Gut microbiome On the baseline, 4th, 8th, 12th week of treatment At baseline, we evaluate the bacterial diversity, different species, different genes, and different metabolic pathways in the BBR+Standard therapy group and the Standard therapy group . In addition, we mainly focused on α and β diversity variation in the remaining 3 visits of BBR+Standard therapy subjucts. Taxonomy alteration and bacterial metabolic pathways after BBR treatment were also observed.
Fecal metabolomics profile measurement On the baseline, 4th, 8th, 12th week of treatment In aid of LC/MS and GC/MS technique, we will measure the metabolomics molecular profile in fecal samples at baseline, 4th, 8th, 12th week. We aimed to detect the profile of short chain fatty acids including Acetic acid, Propanoic acid, Isobutyric acid, Butyric acid, Ethylmethylacetic acid, Isovaleric acid, Valeric acid, 2-methylvaleric acid, 3-methylvaleric acid, 4-methylvaleric acid, Hexanoic acid-SCFA and 3_Hydroxyisovaleric acid.
Endothelial function measured by Flow mediated dilation (FMD) On the baseline, 4th, 8th, 12th week of treatment Flow-mediated vasodilation measurement in the brachial artery was performed with subjects in the supine position for the evaluation of endothelial function. All imaging was performed by a single, highly skilled sonographer who was unaware of the study assignment.brachial artery diameter was imaged with a 5-12-MHz linear array transducer ultrasound system at a location 3 to 7 cm above the right elbow. The brachial artery diameters at baseline (D0) and after reactive hyperemia (D1) and sublingual nitroglycerine (D2) were recorded. The flow-mediated vasodilation \[(D1-D0)/D0×100%\] was used as a measure of endothelium-dependent vasodilation.
- Secondary Outcome Measures
Name Time Method Inflammatory factor levels On the 12th week of treatment hs-CRP (mg/L), IL-1b (pg/mL), IL-6 (pg/mL), IL-18 (pg/mL), TNF-a (pg/mL), IFN-r (pg/mL), IL-10 (pg/mL).
Blood glucose levels On the baseline, 4th, 8th, 12th week of treatment Fasting glucose level (mmol/L), 2-hour postprandial glucose levels (mmol/L), HbA1c %.
Blood lipid levels On the baseline, 4th, 8th, 12th week of treatment Total cholesterol (mmol/L), Triglyceride (mmol/L), HDL-C (mmol/L), LDL-C (mmol/L), Free fatty acids (umol/L), ApoA1(g/L), ApoB (g/L), Lp(a) (mg/L).
Trial Locations
- Locations (1)
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China