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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-I2M-1-011 | Other Grant/Funding Number | CAMS Innovation Fund for Medical Sciences (CIFMS) |
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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Berberine+standard therapy Arm | Experimental | 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. |
|
| Standard therapy Arm | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Berberine | Drug | 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). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Endothelial function measured by Flow mediated dilation (FMD) | 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 | 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 | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Blood lipid levels | 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 |
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Inclusion Criteria:
Patients with stable coronary artery disease undergo elective PCI >8 weeks, but ≤40 weeks
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ran Tian, M.D. | Peking Union Medical College Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking Union Medical College Hospital | Beijing | Beijing Municipality | 100730 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24299895 | Background | 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. | |
| 1359209 | Background |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Jul 14, 2020 | |
| Reset | Jul 30, 2020 |
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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.
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| Aspirin | Drug | Aspirin 100 mg once daily for 12±1 weeks. |
|
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| Clopidogrel | Drug | Clopidogrel 75 mg once daily for 12±1 weeks. |
|
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| Statin | Drug | Statins once daily for 12±1 weeks. |
|
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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 | Fasting glucose level (mmol/L), 2-hour postprandial glucose levels (mmol/L), HbA1c %. | On the baseline, 4th, 8th, 12th week of treatment |
| 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. |
| 22972297 | Background | 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. |
| 26567372 | Background | 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. |
| 23212374 | Background | 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. |
| 19699071 | Background | 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. |
| 21915347 | Background | 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. |
| 28403947 | Background | 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. |
| 26923892 | Background | 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. |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Jul 14, 2020 | Jul 30, 2020 |
| ID | Term |
|---|---|
| D001599 | Berberine |
| D001241 | Aspirin |
| D000077144 | Clopidogrel |
| D019161 | Hydroxymethylglutaryl-CoA Reductase Inhibitors |
| D000069059 | Atorvastatin |
| D000068718 | Rosuvastatin Calcium |
| ID | Term |
|---|---|
| D001600 | Berberine Alkaloids |
| D044182 | Benzylisoquinolines |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000924 | Anticholesteremic Agents |
| D000960 | Hypolipidemic Agents |
| D000963 | Antimetabolites |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D004791 | Enzyme Inhibitors |
| D057847 | Lipid Regulating Agents |
| D045506 | Therapeutic Uses |
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006538 | Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D013450 | Sulfones |
| D011743 | Pyrimidines |
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