Clinical trial NCT04434365: Effect of Berberine for Endothelial Function and Intestinal Microflora in Patients With Coronary Artery Disease
Official title: The Study of Berberine Affecting Metabolism, Inflammation Status, Endothelial Function and Thrombotic Events in Patients With Coronary Artery Disease by Remodeling Gut Microbiota
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Stable Coronary Artery Disease
Percutaneous Coronary Intervention
Keywords: Berberine
Gut microbiota
Endothelial function
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2020-06-16
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Endothelial function measured by Flow mediated dilation (FMD)
timeFrame: On the baseline, 4th, 8th, 12th week of treatment
measure: Gut microbiome
timeFrame: On the baseline, 4th, 8th, 12th week of treatment
measure: Fecal metabolomics profile measurement
timeFrame: On the baseline, 4th, 8th, 12th week of treatment
Secondary outcomes:
measure: Blood lipid levels
timeFrame: On the baseline, 4th, 8th, 12th week of treatment
measure: Inflammatory factor levels
timeFrame: On the 12th week of treatment
measure: Blood glucose levels
timeFrame: On the baseline, 4th, 8th, 12th week of treatment
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Ran Tian, M.D.
role: PRINCIPAL_INVESTIGATOR
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