Berberine Hyperglycemic Clamp (BBR HC)

Effect of Berberine on Insulin Release at a High Blood Glucose Level in Normal Man

Berberine (BBR) is a traditional Chinese medicine used to treat diabetes mellitus for thousands of years in China. The glucose-lowering effect of BBR has been confirmed in numerous studies. Nevertheless, the detailed mechanisms of action through which BBR exerts its effects are not yet fully elucidated. In previous data, Jin-Kui Yang found that BBR could promote insulin secretion in mice and isolated islets. In this current study, investigators plan to examine the insulinotropic effect of BBR in human through hyperglycemic clamp method.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: Berberine Chloride; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Beijing Tongren Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Adult healthy male, aged ≥18 and ≤45 years old.
2. Subject/ legal representative is able to understand and sign informed consent form.
3. Body mass index (BMI) 18-25 kg/m2.
4. Normal oral glucose tolerance test prior to study.
5. No family history of diabetes mellitus.
6. No medication treatment within 4 weeks prior to baseline visit and during the study.
7. Willing and able to comply with all study-related procedures, including not incorporating significant changes in diet.

Exclusion Criteria:

1. Infection with hepatitis (A, B, or C), HIV and syphilis.
2. History of allergic reaction to berberine or any component in the formulation of the study drugs.
3. Cumulative amount of blood loss (eg. blood donation) over 400mL within 3 months prior to baseline visit and during the study.
4. Alcohol drinking within 2 weeks prior to baseline visit and during the study.
5. Use of illegal drugs or positive in urine drugs screen.
6. Smoke during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo control	Drug: Berberine Chloride; Traditional Chinese Medicine; Drug: Placebo; Placebo Control
Experimental: Berberine treatment	Drug: Berberine Chloride; Traditional Chinese Medicine; Drug: Placebo; Placebo Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences of serum insulin levels between BBR and placebo treatment groups during the 2-hour hyperglycemic clamp study.	To compare the mean serum insulin levels in the two groups during hyperglycemic clamp study.	Single dosage for one experiment and crossover repeat once after 2 weeks washout period
Differences of serum C-peptide levels between BBR and placebo treatment groups during the 2-hour hyperglycemic clamp study.	To compare the mean serum C-peptide levels in the two groups during hyperglycemic clamp study.	Single dosage for one experiment and crossover repeat once after 2 weeks washout period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences of glucose infusion rates between BBR and placebo treatment groups during the 2-hour hyperglycemic clamp study.	To compare the mean glucose infusion rates in the two groups during hyperglycemic clamp study.	Single dosage for one experiment and crossover repeat once after 2 weeks washout period
Differences of blood glucose levels between BBR and placebo treatment groups during the 2-hour hyperglycemic clamp study.	To compare the mean blood glucose levels in the two groups during hyperglycemic clamp study.	Single dosage for one experiment and crossover repeat once after 2 weeks washout period

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate and QT-interval duration using electrocardiogram before and after drug treatment.	Electrocardiogram will be performed in subjects before and after drug treatment.	Single dosage for one experiment and crossover repeat once after 2 weeks washout period

Collaborators and Investigators

• Sponsor: Jin-Kui Yang

Publications and helpful links

General Publications

• Zhao MM, Lu J, Li S, Wang H, Cao X, Li Q, Shi TT, Matsunaga K, Chen C, Huang H, Izumi T, Yang JK. Berberine is an insulin secretagogue targeting the KCNH6 potassium channel. Nat Commun. 2021 Sep 23;12(1):5616. doi: 10.1038/s41467-021-25952-2. Erratum In: Nat Commun. 2021 Oct 29;12(1):6342.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Actual): January 20, 2020
• Study Completion (Actual): February 17, 2020

Study Registration Dates

• First Submitted: May 29, 2019
• First Submitted That Met QC Criteria: May 30, 2019
• First Posted (Actual): June 3, 2019

Study Record Updates

• Last Update Posted (Actual): July 10, 2023
• Last Update Submitted That Met QC Criteria: July 7, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Hyperglycemic Clamp
• Other Study ID Numbers: BBR CLAMP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No