NCT03438292

Brief Summary

Berberine from medicinal plants has therapeutic activities against multiple chronic diseases. But its absorption rate is very low. The objective of this study is to test if adding TPGS or Quillaja extract as an emulsifier enhance the absorption of berberine in human.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
32

participants targeted

Target at P25-P50 for not_applicable healthy

Timeline
Completed

Started Sep 2018

Typical duration for not_applicable healthy

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 5, 2018

Completed
14 days until next milestone

First Posted

Study publicly available on registry

February 19, 2018

Completed
7 months until next milestone

Study Start

First participant enrolled

September 25, 2018

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 11, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 11, 2020

Completed
Last Updated

January 27, 2021

Status Verified

January 1, 2021

Enrollment Period

2 years

First QC Date

February 5, 2018

Last Update Submit

January 26, 2021

Conditions

Healthy

Keywords

BerberineTPGSPharmacokineticsHuman intervention studyQuillaja extract

Outcome Measures

Primary Outcomes (3)

  • AUC:the area under the concentration-time curve

    To determine change in bioavailability of orally ingested berberine in human volunteers by increasing the area under the concentration-time curve (AUC).

    Pre-dose, Hour 0.5, Hour 1, Hour 2, Hour 3, Hour 4, Hour 6, Hour 8 and Hour 12

  • Cmax: maximum plasma concentration

    To determine change in bioavailability of orally ingested berberine in human volunteers by increasing its plasma concentration peak concentration (Cmax).

    Pre-dose, Hour 0.5, Hour 1, Hour 2, Hour 3, Hour 4, Hour 6, Hour 8 and Hour 12

  • Tmax: the time point of maximum plasma concentration

    To determine change in bioavailability of orally ingested berberine in human volunteers by increasing its the time point of maximum plasma concentration (Tmax).

    Pre-dose, Hour 0.5, Hour 1, Hour 2, Hour 3, Hour 4, Hour 6, Hour 8 and Hour 12

Secondary Outcomes (1)

  • Changes in concentrations of berberine metabolites.

    Pre-dose, Hour 0.5, Hour 1, Hour 2, Hour 3, Hour 4, Hour 6, Hour 8 and Hour 12

Study Arms (3)

Group A - TPGS emulsified with berberine

EXPERIMENTAL

After an 8-10 hour overnight fast, Group A will receive two soft capsules of TPGS (400mg) emulsified berberine. Following a 7 day wash out period, Group A participants will then receive four capsules of the Quillaja extract emulsified berberine (200mg). Following another 7 day wash out period, Group A participants will then receive two hard shell capsules of the berberine reference powder 400mg. Each TPGS and berberine reference powder capsules contains 400 mg berberine. Each Quillaja extract capsule contains 200 mg berberine. The total amount of berberine throughout is 800 mg.

Dietary Supplement: BerberineDietary Supplement: TPGS emulsified berberineDietary Supplement: Quillaja extract emulsified berberine

Group B - Quillaja extract emulsified with Berberine

EXPERIMENTAL

After an 8-10 hour overnight fast, Group B will receive four soft capsules of Quillaja extract emulsified berberine (400mg). Following a 7 day wash out period, Group B participants will then receive two hard shell capsules of the berberine reference powder (400mg). Following another 7 day wash out period, Group B participants will then receive two soft gel capsules of TPGS emulsified berberine (400mg). Each TPGS and berberine reference powder capsules contains 400 mg berberine. Each Quillaja extract capsule contains 200mg berberine. The total amount of berberine throughout is 800 mg.

Dietary Supplement: BerberineDietary Supplement: TPGS emulsified berberineDietary Supplement: Quillaja extract emulsified berberine

Group C - Berberine reference powder

EXPERIMENTAL

After an 8-10 hour overnight fast, Group C will receive two hard shell capsules of the berberine reference powder (400mg). Following a 7 day wash out period, Group C participants will then receive two soft gel capsules of TPGS emulsified berberine (400mg). Following another 7 day wash out period, Group C participants will then receive four capsules of the Quillaja extract emulsified berberine (200mg). Each TPGS and berberine reference powder capsules contains 400 mg berberine. Each Quillaja extract capsule contains 200mg berberine. The total amount of berberine throughout is 800 mg.

Dietary Supplement: BerberineDietary Supplement: TPGS emulsified berberineDietary Supplement: Quillaja extract emulsified berberine

Interventions

BerberineDIETARY_SUPPLEMENT

Two capsules of berberine. Each capsule contains 400 mg berberine. The total amount of berberine throughout is 800 mg.

Group A - TPGS emulsified with berberineGroup B - Quillaja extract emulsified with BerberineGroup C - Berberine reference powder
TPGS emulsified berberineDIETARY_SUPPLEMENT

Two capsules of TPGS/Quillaja extract emulsified berberine. Each capsule contains 400 mg berberine. The total amount of berberine throughout is 800 mg.

Also known as: Berb-Evail
Group A - TPGS emulsified with berberineGroup B - Quillaja extract emulsified with BerberineGroup C - Berberine reference powder
Quillaja extract emulsified berberineDIETARY_SUPPLEMENT

Four capsules of Quillaja extract emulsified berberine. Each capsule contains 200 mg berberine. The total amount of berberine throughout is 800 mg.

Group A - TPGS emulsified with berberineGroup B - Quillaja extract emulsified with BerberineGroup C - Berberine reference powder

Eligibility Criteria

Age21 Years - 50 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Healthy
  • Normal BMI (20-27)

You may not qualify if:

  • Pregnancy
  • Gastro-intestinal conditions
  • Diabetics,
  • Alcohol and substance abuse history,
  • Allergy to berberine,
  • Current berberine use,
  • Use of H2 blockers, proton pump inhibitors, blood sugar-lowering agents, or statins

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Food Science and human nutrition department at University of Florida

Gainesville, Florida, 32611, United States

Location

Related Publications (7)

  • Cai Z, Wang C, Yang W. Role of berberine in Alzheimer's disease. Neuropsychiatr Dis Treat. 2016 Oct 3;12:2509-2520. doi: 10.2147/NDT.S114846. eCollection 2016.

    PMID: 27757035BACKGROUND

  • Pirillo A, Catapano AL. Berberine, a plant alkaloid with lipid- and glucose-lowering properties: From in vitro evidence to clinical studies. Atherosclerosis. 2015 Dec;243(2):449-61. doi: 10.1016/j.atherosclerosis.2015.09.032. Epub 2015 Sep 30.

    PMID: 26520899BACKGROUND

  • Zou K, Li Z, Zhang Y, Zhang HY, Li B, Zhu WL, Shi JY, Jia Q, Li YM. Advances in the study of berberine and its derivatives: a focus on anti-inflammatory and anti-tumor effects in the digestive system. Acta Pharmacol Sin. 2017 Feb;38(2):157-167. doi: 10.1038/aps.2016.125. Epub 2016 Dec 5.

    PMID: 27917872BACKGROUND

  • 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: 28403947BACKGROUND

  • Xu JH, Liu XZ, Pan W, Zou DJ. Berberine protects against diet-induced obesity through regulating metabolic endotoxemia and gut hormone levels. Mol Med Rep. 2017 May;15(5):2765-2787. doi: 10.3892/mmr.2017.6321. Epub 2017 Mar 14.

    PMID: 28447763BACKGROUND

  • Zou T, Gu L. TPGS emulsified zein nanoparticles enhanced oral bioavailability of daidzin: in vitro characteristics and in vivo performance. Mol Pharm. 2013 May 6;10(5):2062-70. doi: 10.1021/mp400086n. Epub 2013 Apr 26.

    PMID: 23557122BACKGROUND

  • Gu S, Cao B, Sun R, Tang Y, Paletta JL, Wu XL, Liu L, Zha W, Zhao C, Li Y, Ridlon JM, Hylemon PB, Zhou H, Aa J, Wang G. Correction: A metabolomic and pharmacokinetic study on the mechanism underlying the lipid-lowering effect of orally administered berberine. Mol Biosyst. 2015 Feb;11(2):664. doi: 10.1039/c4mb90042a. Epub 2014 Dec 23.

    PMID: 25535027BACKGROUND

MeSH Terms

Interventions

Berberine

Intervention Hierarchy (Ancestors)

Berberine AlkaloidsBenzylisoquinolinesAlkaloidsHeterocyclic CompoundsHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-Ring

Study Officials

  • Liwei Gu, PhD

    Univerisity of Florida

    PRINCIPAL INVESTIGATOR

  • Yavuz Yagiz, PhD

    Univerisity of Florida

    STUDY DIRECTOR

  • Gary P Wang, MD PhD, FIDSA

    Univerisity of Florida

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 5, 2018

First Posted

February 19, 2018

Study Start

September 25, 2018

Primary Completion

September 11, 2020

Study Completion

September 11, 2020

Last Updated

January 27, 2021

Record last verified: 2021-01

Locations

US(1)