Effect of Berberine for Endothelial Function and Intestinal Microflora in Patients With Coronary Artery Disease

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Percutaneous Coronary Intervention; Stable Coronary Artery Disease

Treatments: Drug: Aspirin; Drug: Statin; Drug: Berberine; Drug: Clopidogrel

Study type: Interventional

Funder types: Other

Identifiers

NCT04434365

BBRCADGM2019

2016-I2M-1-011

Details and patient eligibility

About

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

Full 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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

Berberine+standard therapy Arm

Experimental group

Description:

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.

Treatment:

Drug: Clopidogrel

Drug: Berberine

Drug: Statin

Drug: Aspirin

Standard therapy Arm

Active Comparator group

Description:

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.

Treatment:

Drug: Clopidogrel

Drug: Statin

Drug: Aspirin