Cardiovascular Risk FactorPhase 2/3NCT03770325
A Mechanistic Randomized Controlled Trial on the Cardiovascular Effect of Berberine
A Phase 2/3 study testing Berberine in people with Cardiovascular Risk Factor, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
Berberine is extracted from Coptis (Huanglian) and Phellodendron Chinese (Huangbai), to make into berberine tablets.1 Recent studies have shown that berberine has beneficial effects on cardiovascular disease (CVD) risk factors,1,2 such as lowering the risk of hyperlipidemia, diabetes, and hypertension.1 In a… Read more about this study
- Who is it for?
- Ages 20 to 65 years, men only
- Conditions the study is for
- Cardiovascular Risk Factor
- What is being tested?
- Berberine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Apr 2019to 1 Nov 2020
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men, who are
- aged 20 to 65 years
- of Chinese ethnicity
- with hyperlipidemia, defined as TG greater than 150 mg/dl (1.70 mmol/L), TC greater than 200 mg/dl (5.16 mmol/L), and/or LDL-c greater than 100 mg/dl (2.58 mmol/L)
- willing to make return visits
- not currently receiving hormone replacement therapy, such as testosterone replacement therapy, in the past 12 months
Show all 11Show fewer
- not currently taking berberine or traditional Chinese medicine that contains berberine, in the past 1 month
- free of any congenital diseases, including familial hypercholesterolemia
- free of any infectious diseases, e.g. seasonal influenza
- free of anemia and glucose-6-phosphate dehydrogenase deficiency
- with no history of any chronic diseases including ischemic heart disease, myocardial infarction (heart attack), stroke, diabetes, cancer, liver/renal dysfunction, and gastrointestinal disorders.
Who cannot join
- All women, and men, who did not meet the aforementioned inclusion criteria, and/or unable or unwilling to provide consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Berberine on Cardiovascular Disease Risk Factors: a Mechanistic Randomized Controlled Trial
Berberine is extracted from Coptis (Huanglian) and Phellodendron Chinese (Huangbai), to make into berberine tablets.1 Recent studies have shown that berberine has beneficial effects on cardiovascular disease (CVD) risk factors,1,2 such as lowering the risk of hyperlipidemia, diabetes, and hypertension.1 In a comprehensive systematic review and meta-analysis of 27 randomized controlled trials (RCTs), berberine effectively reduced low density lipoprotein cholesterol (LDL-c) (-0.65 mmol/L, 95% confidence interval (CI) -0.75 to -0.56), triglycerides (TG) (-0.39 mmol/L, 95% CI -0.59 to -0.19), total cholesterol (TC) (-0.66 mmol/L, 95% CI -1.02 to -0.31) and increased high density lipoprotein cholesterol (HDL-c) (0.07mmol/L, 95% CI 0.04 to 0.1).1 Notably, no serious adverse event has been reported in these trials,1 suggesting a good tolerability of berberine. The mechanism by which berberine exerts a protective role in atherosclerosis is unclear. Protoberberines have been identified as a new inhibitor of AKR1C3, an enzyme responsible for the regulation of steroid hormone action.3 The investigators propose to examine the effects of berberine on a set of well-established CVD risk factors including lipids, systolic and diastolic blood pressure, coagulation factors, adiposity, fasting glucose, insulin, and liver function, as well as to examine potential mediation via testosterone and/or sex hormone binding globulin using a mechanistic, randomized, double-blind, placebo-controlled trial in Chinese men with hyperlipidemia.
Read the detailed description
Objectives: to assess the effect of berberine on a set of well-established CVD risk factors, including lipids, systolic and diastolic blood pressure, coagulation factors, fasting glucose, insulin, adiposity (body mass index (BMI) and waist-hip ratio (WHR)) and the mediation via testosterone and/or sex hormone binding globulin using a mechanistic, parallel RCT.
Study design: a mechanistic, randomized, double-blind, placebo-controlled, parallel trial in 84 Chinese men in Hong Kong.
Interventions: the eligible participants will be randomized to take berberine (500 mg orally twice a day) or placebo for 12 weeks. Blood samples will be taken at baseline, 8-week and 12-week intervention.
Data analysis and expected results: the investigators will use an intention to treat analysis, with multiple imputation for missing data. The investigators will compare the baseline characteristics of participants in the two arms using analysis of variance. The investigators will assess the effects of berberine on changes in CVD risk factors using analysis of variance, and the mediation using causal mediation analysis. Compared to the placebo group, the participants receiving berberine are expected to have lower burden of cardiovascular disease risk factors at the end of the intervention. These effects may be mediated or partly mediated by lowering testosterone.
- Conditions
- Cardiovascular Risk Factor
- Being tested
- Berberine, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BerberineDrug
Purified berberine (500 mg orally twice a day) in tablets for 12 weeks
PlaceboDrug
Placebo tablets, prepared with the same appearance, for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Berberine | Experimental | berberine (500 mg orally twice a day) Receives: Drug: Berberine |
| Placebo | Placebo comparator | placebo (500 mg orally twice a day) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
lipid profile
LDL-cholesterol, HDL-cholesterol, triglycerides and total cholesterol in mmol/L
Measured: change from baseline lipid profile at 8 weeks
lipid profile
LDL-cholesterol, HDL-cholesterol, triglycerides and total cholesterol in mmol/L
Measured: change from baseline lipid profile at 12 weeks
blood pressure
systolic blood pressure and diastolic blood pressure in mmHg
Measured: change from baseline blood pressure at 8 weeks
blood pressure
systolic blood pressure and diastolic blood pressure in mmHg
Measured: change from baseline blood pressure at 12 weeks
thromboxane A2
thromboxane A2 in mmol/L
Measured: change from baseline thromboxane A2 at 8 weeks
thromboxane A2
thromboxane A2 in mmol/L
Measured: change from baseline thromboxane A2 at 12 weeks
testosterone
testosterone in mmol/L
Measured: change from baseline testosterone at 8 weeks
testosterone
testosterone in mmol/L
Measured: change from baseline testosterone at 12 weeks
body mass index (BMI)
weight and height will be combined to report BMI in kg/m^2
Measured: change from baseline body mass index at 8 weeks
body mass index (BMI)
weight and height will be combined to report BMI in kg/m^2
Measured: change from baseline body mass index at 12 weeks
waist hip ratio
waist circumstance and hip circumstance will be combined to report waist hip ratio
Measured: change from baseline waist hip ratio at 8 weeks
waist hip ratio
waist circumstance and hip circumstance will be combined to report waist hip ratio
Measured: change from baseline waist hip ratio at 12 weeks
fasting glucose
fasting glucose in mmol/L
Measured: change from baseline fasting glucose at 8 weeks
fasting glucose
fasting glucose in mmol/L
Measured: change from baseline fasting glucose at 12 weeks
fasting insulin
fasting insulin in mmol/L
Measured: change from baseline fasting insulin at 8 weeks
fasting insulin
fasting insulin in mmol/L
Measured: change from baseline fasting insulin at 12 weeks
liver function
Alanine transaminase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), total bilirubin, Gamma-glutamyltransferase, total protein and albumin in mmol/L
Measured: change from baseline fasting insulin at 8 weeks
liver function
Alanine transaminase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), total bilirubin, Gamma-glutamyltransferase, total protein and albumin in mmol/L
Measured: change from baseline fasting insulin at 12 weeks
sex hormone binding globulin (SHBG)
SHBG in nmol/L
Measured: change from baseline SHBG at 8 weeks
sex hormone binding globulin (SHBG)
SHBG in nmol/L
Measured: change from baseline SHBG at 12 weeks
thrombin time
thrombin time in sec
Measured: change from baseline thrombin time at 8 weeks
thrombin time
thrombin time in sec
Measured: change from baseline thrombin time at 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2018
- Study start1 Apr 2019
- Primary completion1 Nov 2020
- Study completion1 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular Risk FactorStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- Food and Health Bureau, Hong Kong
- Responsible party
- Sponsor
- Investigators
- Jie Zhao, PhD, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03770325
- Sponsor's protocol ID
- 15162621
- Status last verified
- Nov 2020
- First submitted
- 3 Dec 2018
- Last updated
- 4 Nov 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Lan J, Zhao Y, Dong F, Yan Z, Zheng W, Fan J, Sun G. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. 2015 Feb 23;161:69-81. doi: 10.1016/j.jep.2014.09.049. Epub 2014 Dec 10.
PubMed 25498346Imanshahidi M, Hosseinzadeh H. Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phytother Res. 2008 Aug;22(8):999-1012. doi: 10.1002/ptr.2399.
PubMed 18618524Skarydova L, Hofman J, Chlebek J, Havrankova J, Kosanova K, Skarka A, Hostalkova A, Plucha T, Cahlikova L, Wsol V. Isoquinoline alkaloids as a novel type of AKR1C3 inhibitors. J Steroid Biochem Mol Biol. 2014 Sep;143:250-8. doi: 10.1016/j.jsbmb.2014.04.005. Epub 2014 Apr 24.
PubMed 24769118Zhao JV, Sarsani V, Chen B, Yun H, Hu J, Liang L. Berberine signature and cardiometabolic diseases using randomized controlled trial, cohort study and Mendelian randomization. NPJ Cardiovasc Health. 2026 Mar 25;3(1):15. doi: 10.1038/s44325-026-00113-w.
PubMed 41882153
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Berberine on Cardiovascular Disease Risk Factors: a Mechanistic Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03770325
- Acronym / sponsor ID
- 15162621
- Conditions
- Cardiovascular Risk Factor
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Collaborators
- Food and Health Bureau, Hong Kong
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- 1 Nov 2020 (actual)
- Study completion
- 1 Nov 2020 (actual)
- First posted
- 10 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Berberine is extracted from Coptis (Huanglian) and Phellodendron Chinese (Huangbai), to make into berberine tablets.1 Recent studies have shown that berberine has beneficial effects on cardiovascular disease (CVD) risk factors,1,2 such as lowering the risk of hyperlipidemia, diabetes, and hypertension.1 In a comprehensive systematic review and meta-analysis of 27 randomized controlled trials (RCTs), berberine effectively reduced low density lipoprotein cholesterol (LDL-c) (-0.65 mmol/L, 95% confidence interval (CI) -0.75 to -0.56), triglycerides (TG) (-0.39 mmol/L, 95% CI -0.59 to -0.19), total cholesterol (TC) (-0.66 mmol/L, 95% CI -1.02 to -0.31) and increased high density lipoprotein cholesterol (HDL-c) (0.07mmol/L, 95% CI 0.04 to 0.1).1 Notably, no serious adverse event has been reported in these trials,1 suggesting a good tolerability of berberine. The mechanism by which berberine exerts a protective role in atherosclerosis is unclear. Protoberberines have been identified as a new inhibitor of AKR1C3, an enzyme responsible for the regulation of steroid hormone action.3 The investigators propose to examine the effects of berberine on a set of well-established CVD risk factors including lipids, systolic and diastolic blood pressure, coagulation factors, adiposity, fasting glucose, insulin, and liver function, as well as to examine potential mediation via testosterone and/or sex hormone binding globulin using a mechanistic, randomized, double-blind, placebo-controlled trial in Chinese men with hyperlipidemia.
Detailed description
Objectives: to assess the effect of berberine on a set of well-established CVD risk factors, including lipids, systolic and diastolic blood pressure, coagulation factors, fasting glucose, insulin, adiposity (body mass index (BMI) and waist-hip ratio (WHR)) and the mediation via testosterone and/or sex hormone binding globulin using a mechanistic, parallel RCT.
Study design: a mechanistic, randomized, double-blind, placebo-controlled, parallel trial in 84 Chinese men in Hong Kong.
Interventions: the eligible participants will be randomized to take berberine (500 mg orally twice a day) or placebo for 12 weeks. Blood samples will be taken at baseline, 8-week and 12-week intervention.
Data analysis and expected results: the investigators will use an intention to treat analysis, with multiple imputation for missing data. The investigators will compare the baseline characteristics of participants in the two arms using analysis of variance. The investigators will assess the effects of berberine on changes in CVD risk factors using analysis of variance, and the mediation using causal mediation analysis. Compared to the placebo group, the participants receiving berberine are expected to have lower burden of cardiovascular disease risk factors at the end of the intervention. These effects may be mediated or partly mediated by lowering testosterone.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Berberine | Experimental | Drug: Berberineberberine (500 mg orally twice a day) |
| Placebo | Placebo comparator | Drug: Placeboplacebo (500 mg orally twice a day) |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Men, who are
Key exclusion criteria (1 listed)
- All women, and men, who did not meet the aforementioned inclusion criteria, and/or unable or unwilling to provide consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BerberinePurified berberine (500 mg orally twice a day) in tablets for 12 weeks | Drug | Berberine |
| PlaceboPlacebo tablets, prepared with the same appearance, for 12 weeks | Drug | Placebo |
Primary outcome
lipid profile
Time frame: change from baseline lipid profile at 8 weeks
LDL-cholesterol, HDL-cholesterol, triglycerides and total cholesterol in mmol/L
lipid profile
Time frame: change from baseline lipid profile at 12 weeks
LDL-cholesterol, HDL-cholesterol, triglycerides and total cholesterol in mmol/L
blood pressure
Time frame: change from baseline blood pressure at 8 weeks
systolic blood pressure and diastolic blood pressure in mmHg
blood pressure
Time frame: change from baseline blood pressure at 12 weeks
systolic blood pressure and diastolic blood pressure in mmHg
thromboxane A2
Time frame: change from baseline thromboxane A2 at 8 weeks
thromboxane A2 in mmol/L
thromboxane A2
Time frame: change from baseline thromboxane A2 at 12 weeks
thromboxane A2 in mmol/L
testosterone
Time frame: change from baseline testosterone at 8 weeks
testosterone in mmol/L
testosterone
Time frame: change from baseline testosterone at 12 weeks
testosterone in mmol/L
body mass index (BMI)
Time frame: change from baseline body mass index at 8 weeks
weight and height will be combined to report BMI in kg/m^2
body mass index (BMI)
Time frame: change from baseline body mass index at 12 weeks
weight and height will be combined to report BMI in kg/m^2
waist hip ratio
Time frame: change from baseline waist hip ratio at 8 weeks
waist circumstance and hip circumstance will be combined to report waist hip ratio
waist hip ratio
Time frame: change from baseline waist hip ratio at 12 weeks
waist circumstance and hip circumstance will be combined to report waist hip ratio
fasting glucose
Time frame: change from baseline fasting glucose at 8 weeks
fasting glucose in mmol/L
fasting glucose
Time frame: change from baseline fasting glucose at 12 weeks
fasting glucose in mmol/L
fasting insulin
Time frame: change from baseline fasting insulin at 8 weeks
fasting insulin in mmol/L
fasting insulin
Time frame: change from baseline fasting insulin at 12 weeks
fasting insulin in mmol/L
liver function
Time frame: change from baseline fasting insulin at 8 weeks
Alanine transaminase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), total bilirubin, Gamma-glutamyltransferase, total protein and albumin in mmol/L
liver function
Time frame: change from baseline fasting insulin at 12 weeks
Alanine transaminase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), total bilirubin, Gamma-glutamyltransferase, total protein and albumin in mmol/L
sex hormone binding globulin (SHBG)
Time frame: change from baseline SHBG at 8 weeks
SHBG in nmol/L
sex hormone binding globulin (SHBG)
Time frame: change from baseline SHBG at 12 weeks
SHBG in nmol/L
thrombin time
Time frame: change from baseline thrombin time at 8 weeks
thrombin time in sec
thrombin time
Time frame: change from baseline thrombin time at 12 weeks
thrombin time in sec
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2020.
- Background: PubMed 25498346Lan J, Zhao Y, Dong F, Yan Z, Zheng W, Fan J, Sun G. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. 2015 Feb 23;161:69-81. doi: 10.1016/j.jep.2014.09.049. Epub 2014 Dec 10.
- Background: PubMed 18618524Imanshahidi M, Hosseinzadeh H. Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phytother Res. 2008 Aug;22(8):999-1012. doi: 10.1002/ptr.2399.
- Background: PubMed 24769118Skarydova L, Hofman J, Chlebek J, Havrankova J, Kosanova K, Skarka A, Hostalkova A, Plucha T, Cahlikova L, Wsol V. Isoquinoline alkaloids as a novel type of AKR1C3 inhibitors. J Steroid Biochem Mol Biol. 2014 Sep;143:250-8. doi: 10.1016/j.jsbmb.2014.04.005. Epub 2014 Apr 24.
- Derived from this study: PubMed 41882153Zhao JV, Sarsani V, Chen B, Yun H, Hu J, Liang L. Berberine signature and cardiometabolic diseases using randomized controlled trial, cohort study and Mendelian randomization. NPJ Cardiovasc Health. 2026 Mar 25;3(1):15. doi: 10.1038/s44325-026-00113-w.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jie Zhao, PhD principal investigator
The University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Berberine in people with Cardiovascular Risk Factor, run by The University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
lipid profile (time frame: change from baseline lipid profile at 8 weeks). The study lists 22 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03770325, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2020.