<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04434365</url>
  </required_header>
  <id_info>
    <org_study_id>BBRCADGM2019</org_study_id>
    <secondary_id>2016-I2M-1-011</secondary_id>
    <nct_id>NCT04434365</nct_id>
  </id_info>
  <brief_title>Effect of Berberine for Endothelial Function and Intestinal Microflora in Patients With Coronary Artery Disease</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking Union Medical College Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peking Union Medical College Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to conduct a single-center, randomized, open-label, controlled,&#xD;
      dose-escalating, parallel-group study, evaluating the effects and change of endothelial&#xD;
      function and gut microbiota after berberine administration in patients with stable coronary&#xD;
      artery disease who are at &gt; 8 but ≤ 40 weeks after elective percutaneous coronary&#xD;
      intervention&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the present study, about 48 patients with stable coronary artery disease who are at &gt; 8&#xD;
      but ≤ 40 weeks after elective percutaneous coronary intervention. The total study duration is&#xD;
      expected to be approximately 14 weeks per patient, including a screening period, a 12±1 week&#xD;
      treatment period, Randomization was computer generated. After screening, eligible subjects&#xD;
      will be randomly assigned into one of the following two groups: Berberine+therapy Arm or&#xD;
      Standard therapy Arm. The primary objective is to determine whether a combination of&#xD;
      berberine and coronary artery disease standard therapy is preferable to either berberine&#xD;
      alone or standard therapy alone.&#xD;
&#xD;
      The visit schedule will be as follows:&#xD;
&#xD;
      Visit 1: Day -7 to Day -1, Screening/Enrolment; Visit 2: Day 1, Randomization/First dose;&#xD;
      Visit 3: Week 4±1, Dose adjustment 1, BBR (100mg, tid); Visit 4: Week 8±1, Dose adjustment 2,&#xD;
      BBR (200mg, tid); Visit 5: Week 12±1, End of Treatment (EOT) /Last dose, BBR (300mg, tid);&#xD;
      Safety visit.&#xD;
&#xD;
      We perform cross-sectional comparisons between the two arms and longitudinal comparisons&#xD;
      within each arm to evaluate the indicators as follows:&#xD;
&#xD;
        1. . Endothelial function, as measured by Flow mediated dilation (FMD) from baseline to&#xD;
           12-week follow-up;&#xD;
&#xD;
        2. . Gut microbiota, as sequenced by metagenomic sequencing from baseline to 12-week&#xD;
           follow-up.&#xD;
&#xD;
      Blood and feces samples will be collected before and after treatment. Flow mediated dilation&#xD;
      (FMD), HbA1C, fasting plasma glucose (FPG), lipids and cholesterol level, inflammatory&#xD;
      factors, amino acids, bile acids and other metabolic related components and parameters will&#xD;
      be measured. Furthermore, the change of gut microbiota will be evaluated too.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">June 21, 2019</start_date>
  <completion_date type="Anticipated">December 30, 2020</completion_date>
  <primary_completion_date type="Actual">November 18, 2019</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <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.&#xD;
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.&#xD;
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.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Endothelial function measured by Flow mediated dilation (FMD)</measure>
    <time_frame>On the baseline, 4th, 8th, 12th week of treatment</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Gut microbiome</measure>
    <time_frame>On the baseline, 4th, 8th, 12th week of treatment</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Fecal metabolomics profile measurement</measure>
    <time_frame>On the baseline, 4th, 8th, 12th week of treatment</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Blood lipid levels</measure>
    <time_frame>On the baseline, 4th, 8th, 12th week of treatment</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammatory factor levels</measure>
    <time_frame>On the 12th week of treatment</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood glucose levels</measure>
    <time_frame>On the baseline, 4th, 8th, 12th week of treatment</time_frame>
    <description>Fasting glucose level (mmol/L), 2-hour postprandial glucose levels (mmol/L), HbA1c %.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Stable Coronary Artery Disease</condition>
  <condition>Percutaneous Coronary Intervention</condition>
  <arm_group>
    <arm_group_label>Berberine+standard therapy Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard therapy Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Berberine</intervention_name>
    <description>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).</description>
    <arm_group_label>Berberine+standard therapy Arm</arm_group_label>
    <other_name>Berberine Hydrochloride Tablets</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin</intervention_name>
    <description>Aspirin 100 mg once daily for 12±1 weeks.</description>
    <arm_group_label>Berberine+standard therapy Arm</arm_group_label>
    <arm_group_label>Standard therapy Arm</arm_group_label>
    <other_name>Aspirin Enteric-coated Tablets</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clopidogrel</intervention_name>
    <description>Clopidogrel 75 mg once daily for 12±1 weeks.</description>
    <arm_group_label>Berberine+standard therapy Arm</arm_group_label>
    <arm_group_label>Standard therapy Arm</arm_group_label>
    <other_name>Clopidogrel Hydrogen Sulphate Tablets</other_name>
    <other_name>Plavix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Statin</intervention_name>
    <description>Statins once daily for 12±1 weeks.</description>
    <arm_group_label>Berberine+standard therapy Arm</arm_group_label>
    <arm_group_label>Standard therapy Arm</arm_group_label>
    <other_name>Atorvastatin</other_name>
    <other_name>Rosuvastatin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients with stable coronary artery disease undergo elective PCI &gt;8 weeks, but ≤40 weeks&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Planned coronary revascularization, including PCI and coronary artery bypass graft&#xD;
             (CABG) during the study period.&#xD;
&#xD;
          2. Subjects with uncontrolled high blood pressure&#xD;
&#xD;
          3. Recent (within 4 weeks) dose adjustment of any standard therapy agents&#xD;
&#xD;
          4. Recent (within 4 weeks) use of berberine&#xD;
&#xD;
          5. History of intolerance to berberine.&#xD;
&#xD;
          6. Cr&gt;1.5mg/dL; ALT level exceeds the upper limit of 3 times&#xD;
&#xD;
          7. Heart failure or LVEF &lt;50%&#xD;
&#xD;
          8. Uncontrolled arrhythmia&#xD;
&#xD;
          9. Pregnancy or lactation&#xD;
&#xD;
         10. Malignant tumor or life expectancy is less than half a year&#xD;
&#xD;
         11. Subjects who can not complete the follow-up&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ran Tian, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking Union Medical College Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Peking Union Medical College Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>You DG, Saravanakumar G, Son S, Han HS, Heo R, Kim K, Kwon IC, Lee JY, Park JH. Dextran sulfate-coated superparamagnetic iron oxide nanoparticles as a contrast agent for atherosclerosis imaging. Carbohydr Polym. 2014 Jan 30;101:1225-33. doi: 10.1016/j.carbpol.2013.10.068. Epub 2013 Oct 26.</citation>
    <PMID>24299895</PMID>
  </reference>
  <reference>
    <citation>Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992 Nov 7;340(8828):1111-5. doi: 10.1016/0140-6736(92)93147-f.</citation>
    <PMID>1359209</PMID>
  </reference>
  <reference>
    <citation>Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012 Sep 13;489(7415):242-9. doi: 10.1038/nature11552.</citation>
    <PMID>22972297</PMID>
  </reference>
  <reference>
    <citation>Matsuzawa Y, Kwon TG, Lennon RJ, Lerman LO, Lerman A. Prognostic Value of Flow-Mediated Vasodilation in Brachial Artery and Fingertip Artery for Cardiovascular Events: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2015 Nov 13;4(11):e002270. doi: 10.1161/JAHA.115.002270.</citation>
    <PMID>26567372</PMID>
  </reference>
  <reference>
    <citation>Karlsson FH, Fak F, Nookaew I, Tremaroli V, Fagerberg B, Petranovic D, Backhed F, Nielsen J. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat Commun. 2012;3:1245. doi: 10.1038/ncomms2266.</citation>
    <PMID>23212374</PMID>
  </reference>
  <reference>
    <citation>Affuso F, Ruvolo A, Micillo F, Sacca L, Fazio S. Effects of a nutraceutical combination (berberine, red yeast rice and policosanols) on lipid levels and endothelial function randomized, double-blind, placebo-controlled study. Nutr Metab Cardiovasc Dis. 2010 Nov;20(9):656-61. doi: 10.1016/j.numecd.2009.05.017. Epub 2009 Aug 20.</citation>
    <PMID>19699071</PMID>
  </reference>
  <reference>
    <citation>Xie W, Gu D, Li J, Cui K, Zhang Y. Effects and action mechanisms of berberine and Rhizoma coptidis on gut microbes and obesity in high-fat diet-fed C57BL/6J mice. PLoS One. 2011;6(9):e24520. doi: 10.1371/journal.pone.0024520. Epub 2011 Sep 6.</citation>
    <PMID>21915347</PMID>
  </reference>
  <reference>
    <citation>Wang Y, Shou JW, Li XY, Zhao ZX, Fu J, He CY, Feng R, Ma C, Wen BY, Guo F, Yang XY, Han YX, Wang LL, Tong Q, You XF, Lin Y, Kong WJ, Si SY, Jiang JD. Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. Metabolism. 2017 May;70:72-84. doi: 10.1016/j.metabol.2017.02.003. Epub 2017 Feb 10.</citation>
    <PMID>28403947</PMID>
  </reference>
  <reference>
    <citation>Cao Y, Pan Q, Cai W, Shen F, Chen GY, Xu LM, Fan JG. Modulation of Gut Microbiota by Berberine Improves Steatohepatitis in High-Fat Diet-Fed BALB/C Mice. Arch Iran Med. 2016 Mar;19(3):197-203.</citation>
    <PMID>26923892</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 27, 2019</study_first_submitted>
  <study_first_submitted_qc>June 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>June 13, 2020</last_update_submitted>
  <last_update_submitted_qc>June 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Berberine</keyword>
  <keyword>Gut microbiota</keyword>
  <keyword>Endothelial function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Coronary Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Clopidogrel</mesh_term>
    <mesh_term>Atorvastatin</mesh_term>
    <mesh_term>Rosuvastatin Calcium</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>July 14, 2020</submitted>
    <returned>July 30, 2020</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04434365
org study id: BBRCADGM2019
secondary id: 2016-I2M-1-011
nct id: NCT04434365
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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
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.
allocation: Randomized
intervention model: Parallel Assignment
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
masking: None (Open Label)
measure: Endothelial function measured by Flow mediated dilation (FMD)
time frame: On the baseline, 4th, 8th, 12th week of treatment
description: 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.
measure: Gut microbiome
time frame: On the baseline, 4th, 8th, 12th week of treatment
description: 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.
measure: Fecal metabolomics profile measurement
time frame: On the baseline, 4th, 8th, 12th week of treatment
description: 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.
measure: Blood lipid levels
time frame: On the baseline, 4th, 8th, 12th week of treatment
description: 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).
measure: Inflammatory factor levels
time frame: On the 12th week of treatment
description: 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).
measure: Blood glucose levels
time frame: On the baseline, 4th, 8th, 12th week of treatment
description: Fasting glucose level (mmol/L), 2-hour postprandial glucose levels (mmol/L), HbA1c %.
arm group label: Berberine+standard therapy Arm
arm group type: Experimental
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.
arm group label: Standard therapy Arm
arm group type: Active Comparator
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.
intervention type: Drug
intervention name: Berberine
description: 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).
arm group label: Berberine+standard therapy Arm
other name: Berberine Hydrochloride Tablets
intervention type: Drug
intervention name: Aspirin
description: Aspirin 100 mg once daily for 12±1 weeks.
arm group label: Berberine+standard therapy Arm
arm group label: Standard therapy Arm
other name: Aspirin Enteric-coated Tablets
intervention type: Drug
intervention name: Clopidogrel
description: Clopidogrel 75 mg once daily for 12±1 weeks.
arm group label: Berberine+standard therapy Arm
arm group label: Standard therapy Arm
other name: Clopidogrel Hydrogen Sulphate Tablets
other name: Plavix
intervention type: Drug
intervention name: Statin
description: Statins once daily for 12±1 weeks.
arm group label: Berberine+standard therapy Arm
arm group label: Standard therapy Arm
other name: Atorvastatin
other name: Rosuvastatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Ran Tian, M.D.
role: Principal Investigator
affiliation: Peking Union Medical College Hospital
facility: 
country: China
citation: You DG, Saravanakumar G, Son S, Han HS, Heo R, Kim K, Kwon IC, Lee JY, Park JH. Dextran sulfate-coated superparamagnetic iron oxide nanoparticles as a contrast agent for atherosclerosis imaging. Carbohydr Polym. 2014 Jan 30;101:1225-33. doi: 10.1016/j.carbpol.2013.10.068. Epub 2013 Oct 26.
PMID: 24299895
citation: Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992 Nov 7;340(8828):1111-5. doi: 10.1016/0140-6736(92)93147-f.
PMID: 1359209
citation: Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012 Sep 13;489(7415):242-9. doi: 10.1038/nature11552.
PMID: 22972297
citation: Matsuzawa Y, Kwon TG, Lennon RJ, Lerman LO, Lerman A. Prognostic Value of Flow-Mediated Vasodilation in Brachial Artery and Fingertip Artery for Cardiovascular Events: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2015 Nov 13;4(11):e002270. doi: 10.1161/JAHA.115.002270.
PMID: 26567372
citation: Karlsson FH, Fak F, Nookaew I, Tremaroli V, Fagerberg B, Petranovic D, Backhed F, Nielsen J. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat Commun. 2012;3:1245. doi: 10.1038/ncomms2266.
PMID: 23212374
citation: Affuso F, Ruvolo A, Micillo F, Sacca L, Fazio S. Effects of a nutraceutical combination (berberine, red yeast rice and policosanols) on lipid levels and endothelial function randomized, double-blind, placebo-controlled study. Nutr Metab Cardiovasc Dis. 2010 Nov;20(9):656-61. doi: 10.1016/j.numecd.2009.05.017. Epub 2009 Aug 20.
PMID: 19699071
citation: Xie W, Gu D, Li J, Cui K, Zhang Y. Effects and action mechanisms of berberine and Rhizoma coptidis on gut microbes and obesity in high-fat diet-fed C57BL/6J mice. PLoS One. 2011;6(9):e24520. doi: 10.1371/journal.pone.0024520. Epub 2011 Sep 6.
PMID: 21915347
citation: Wang Y, Shou JW, Li XY, Zhao ZX, Fu J, He CY, Feng R, Ma C, Wen BY, Guo F, Yang XY, Han YX, Wang LL, Tong Q, You XF, Lin Y, Kong WJ, Si SY, Jiang JD. Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. Metabolism. 2017 May;70:72-84. doi: 10.1016/j.metabol.2017.02.003. Epub 2017 Feb 10.
PMID: 28403947
citation: Cao Y, Pan Q, Cai W, Shen F, Chen GY, Xu LM, Fan JG. Modulation of Gut Microbiota by Berberine Improves Steatohepatitis in High-Fat Diet-Fed BALB/C Mice. Arch Iran Med. 2016 Mar;19(3):197-203.
PMID: 26923892
responsible party type: Sponsor
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Coronary Disease
mesh term: Aspirin
mesh term: Clopidogrel
mesh term: Atorvastatin
mesh term: Rosuvastatin Calcium
submitted: July 14, 2020
returned: July 30, 2020