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

June 13, 2020 updated by: Peking Union Medical College Hospital

The Study of Berberine Affecting Metabolism, Inflammation Status, Endothelial Function and Thrombotic Events in Patients With Coronary Artery Disease by Remodeling Gut Microbiota

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100730
        • Peking Union Medical College Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Berberine+standard therapy Arm
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.
Drug: Aspirin
Aspirin 100 mg once daily for 12±1 weeks.
Other Names:
  • Aspirin Enteric-coated Tablets
Drug: Clopidogrel
Clopidogrel 75 mg once daily for 12±1 weeks.
Other Names:
  • Plavix
  • Clopidogrel Hydrogen Sulphate Tablets
Drug: Berberine
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).
Other Names:
  • Berberine Hydrochloride Tablets
Drug: Statin
Statins once daily for 12±1 weeks.
Other Names:
  • Rosuvastatin
  • Atorvastatin
Active Comparator: Standard therapy Arm
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.
Drug: Aspirin
Aspirin 100 mg once daily for 12±1 weeks.
Other Names:
  • Aspirin Enteric-coated Tablets
Drug: Clopidogrel
Clopidogrel 75 mg once daily for 12±1 weeks.
Other Names:
  • Plavix
  • Clopidogrel Hydrogen Sulphate Tablets
Drug: Statin
Statins once daily for 12±1 weeks.
Other Names:
  • Rosuvastatin
  • Atorvastatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endothelial function measured by Flow mediated dilation (FMD)
Time Frame: 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.
On the baseline, 4th, 8th, 12th week of treatment
Gut microbiome
Time Frame: 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.
On the baseline, 4th, 8th, 12th week of treatment
Fecal metabolomics profile measurement
Time Frame: 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.
On the baseline, 4th, 8th, 12th week of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Blood lipid levels
Time Frame: 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).
On the baseline, 4th, 8th, 12th week of treatment
Inflammatory factor levels
Time Frame: 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).
On the 12th week of treatment
Blood glucose levels
Time Frame: On the baseline, 4th, 8th, 12th week of treatment
Fasting glucose level (mmol/L), 2-hour postprandial glucose levels (mmol/L), HbA1c %.
On the baseline, 4th, 8th, 12th week of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking Union Medical College Hospital

Investigators

  • Principal Investigator: Ran Tian, M.D., Peking Union Medical College Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 21, 2019

Primary Completion (Actual)

November 18, 2019

Study Completion (Anticipated)

December 30, 2020

Study Registration Dates

First Submitted

June 27, 2019

First Submitted That Met QC Criteria

June 13, 2020

First Posted (Actual)

June 16, 2020

Study Record Updates

Last Update Posted (Actual)

June 16, 2020

Last Update Submitted That Met QC Criteria

June 13, 2020

Last Verified

June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BBRCADGM2019
  • 2016-I2M-1-011 (CAMS Innovation Fund for Medical Sciences (CIFMS))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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