Percutaneous Coronary Intervention, Stable Coronary Artery Disease
Conditions
Keywords
Berberine, Gut microbiota, Endothelial function
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.
Interventions
DRUGBerberine
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 weeks (Stage 3).
DRUGAspirin
Aspirin 100 mg once daily for 12±1 weeks.
DRUGClopidogrel
Clopidogrel 75 mg once daily for 12±1 weeks.
DRUGStatin
Statins once daily for 12±1 weeks.
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
On the first day of the treatment period (Visit 1), eligible patients will be randomized into the Berberine Arm and the Control Arm. In the Berberine Arm, patients will receive berberine 200 mg twice daily for 4±1 weeks (Stage 1); then, 300 mg twice daily for 4±1 weeks (Stage 2); then, 400 mg twice daily for 4±1 weeks (Stage 3) in addition to standard treatment, including aspirin 100 mg once daily and clopidogrel 75 mg once daily for 12±1 weeks. In the Control Arm, patients will receive standard treatment, including aspirin 100 mg once daily and clopidogrel 75 mg once daily for 12±1 weeks.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Patients with stable coronary artery disease undergo elective PCI \>8 weeks, but ≤40 weeks
Exclusion criteria
1. Planned coronary revascularization, including PCI and coronary artery bypass graft (CABG) during the study period. 2. Subjects with uncontrolled high blood pressure 3. Recent (within 4 weeks) dose adjustment of any standard therapy agents 4. Recent (within 4 weeks) use of berberine 5. History of intolerance to berberine. 6. Cr\>1.5mg/dL; ALT level exceeds the upper limit of 3 times 7. Heart failure or LVEF \<50% 8. Uncontrolled arrhythmia 9. Pregnancy or lactation 10. Malignant tumor or life expectancy is less than half a year 11. Subjects who can not complete the follow-up
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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 %. |
Countries
China
Outcome results
None listed