Effect of Gamma-cyclodextrin on the Bioavailability of Berberine

NCT ID: NCT04918667

Last Updated: 2023-09-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-30

Study Completion Date

2026-12-31

Brief Summary

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In this study, we will evaluate the relative bioavailability of Berberine (BB) from capsules containing Indian Barberry (Berberis aristate DC.) Bark and Root Extract in the blood plasma of healthy subjects after oral administration of:

A. Capsules containing Berberine and GCD (BBA Berberine MetX™ Ultra Absorption, 250 mg) B. Capsules containing Berberine (BB, Berberine MetX™, 500 mg) - (reference product).

Detailed Description

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Study Background

A growing body of evidence suggests that gamma-cyclodextrin (GCD) can increase the clinical efficacy of water-insoluble biologically active compounds with low bioavailability. GCD is the most bio adaptable and helpful to increase the absorption of many drugs, including Berberine from Indian Barberry (Berberis aristate DC.) Bark and Root Extract by forming inclusion complexes or GCD/drug conjugates.

Berberine has been recommended in traditional practice and recognized by modern science to support healthy blood sugar†, cholesterol and triglyceride levels, and overall metabolic health. But despite these findings, standard Berberine can still be difficult for the body to absorb and use effectively.

It's estimated that only about five percent of any given dosage of Berberine makes it into the bloodstream, so finding a way to enhance absorption is key to the full advantage of its benefits.

Hypothesis: gamma-cyclodextrin increases absorption and bioavailability of Berberine from Berberine MetX™ Ultra Absorption capsules.

The study aims to provide experimental evidence supporting or rejecting this hypothesis.

This will be a double-blind, crossover design, pharmacokinetic study, where 16 healthy human volunteers will be randomly assigned to receive two different formulations BBA, and BB, in two consecutive phases of the study:

* Phase A. All patients take capsules BBA., provide blood samples in 0.5, 0.75, 1, 2, 4, 6, 12, 24, and 48 hours (9 points) after administration following washout period for two weeks.
* Phase B. All patients take capsules BB, provide blood samples in 0.5, 0.75, 1, 2, 4, 6, 12, 24, and 48 hours (9 points) after administration following washout period for two weeks.

Subjects will be in the clinic from not less than 11 hours pre-dose to ensure at least 10 hours fasting before administering the investigational product. They will remain in the facility post-dose until at least 24 hours each period, provided they are not suffering from any adverse event.

The concentration of Berberine in all blood samples will be determined using a validated for a limit of detection, accuracy, and precision analytical method (HPLC-MS) with the internal standard - digoxin. Appropriate mathematical methods and Kinetic 4.4.1 software will be used to generate basic pharmacokinetic parameters.

Conditions

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Drug Absorption

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Berberine MetX™ Ultra Absorption

16 healthy subjects will receive orally 500 mg of berberine in two capsules of Berberine MetX™ Ultra Absorption.

Group Type EXPERIMENTAL

Berberine incorporated in gamma cyclodextrin

Intervention Type COMBINATION_PRODUCT

Experimental modified product. One capsule contains 250 mg of Berberine from Indian Barberry (Berberis aristate DC.) Bark and Root Extract incorporated in gamma-cyclodextrin

Berberine MetX™

16 healthy subjects will receive orally 500 mg of berberine in one capsule of Berberine MetX™ (reference product).

Group Type ACTIVE_COMPARATOR

Berberine

Intervention Type DIETARY_SUPPLEMENT

Active comparator. One capsule contains 500 mg of Berberine from Indian Barberry (Berberis aristate DC.) Bark and Root Extract

Interventions

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Berberine incorporated in gamma cyclodextrin

Experimental modified product. One capsule contains 250 mg of Berberine from Indian Barberry (Berberis aristate DC.) Bark and Root Extract incorporated in gamma-cyclodextrin

Intervention Type COMBINATION_PRODUCT

Berberine

Active comparator. One capsule contains 500 mg of Berberine from Indian Barberry (Berberis aristate DC.) Bark and Root Extract

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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Berberine MetX™ Ultra Absorption, 250 mg Berberine MetX™, 500 mg

Eligibility Criteria

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Inclusion Criteria

* Healthy volunteers, as determined by medical history, physical examination, and clinical laboratory testing,
* Willingness to stay in the unit overnight for the duration of the study,
* Provide a signed written informed consent.

Exclusion Criteria

* overweight (BMI \>35 kg/m2),
* pregnancy,
* lactation,
* drug abuse,
* use of dietary supplements or any form of medication (with the exception of oral contraceptives),
* heavy smokers, or ex-smokers with a remote history (\> one pack/day),
* frequent alcohol consumption (\>20 g ethanol/d),
* adherence to a restrictive dietary regimen,
* physical activity of more than 5 h/wk,
* respiratory tract infections, or suspicion thereof in the last 14 days before dosing,
* history or presence of disease in the kidneys and heart, lungs, liver, gastrointestinal tract, endocrine organs or other conditions such as metabolic disease known to interfere with the absorption, distribution, metabolism, and excretion of drugs,
* malignancy,
* autoimmune disorders such as (but not limited to) lupus erythematosus, multiple sclerosis, rheumatoid arthritis, or sarcoidosis,
* any other disease or condition, which, in the opinion of the Investigator, would make the subject unsuitable for this study,
* currently taking medications known to be CYP2C9 inducers (i.e., carbamazepine and rifampicin).
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Scientific Center of Drug and Medical Technologies Expertise of the Ministry of Health, Armenia

UNKNOWN

Sponsor Role collaborator

Cardiomed LLC, Armenia

UNKNOWN

Sponsor Role collaborator

Institute of Fine Organic Chemistry of the National Academy of Science, Armenia

UNKNOWN

Sponsor Role collaborator

Phytomed AB, Sweden

UNKNOWN

Sponsor Role collaborator

EuroPharma, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Aghavni Ginosyan, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Scientific Center of Drug and Medical Technologies Expertise of the Ministry of Health, Armenia

Samvel Hairumyan, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

CARDIOMED Family Health Center, LLC of the Ministry of Health of the Republic of Armenia

Areg Hovhannisyan, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Fine Organic Chemistry of the National Academy of Science, Armenia

Alexander G Panossian, PhD

Role: STUDY_DIRECTOR

Phytomed AB, Sweden

Locations

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CARDIOMED Family Health Center, LLC of the Ministry of Health of the Republic of Armenia

Yerevan, , Armenia

Site Status

Institute of Fine Organic Chemistry of the National Academy of Science

Yerevan, , Armenia

Site Status

Scientific Center of Drug and Medical Technologies Expertise

Yerevan, , Armenia

Site Status

Phytomed AB

Våxtorp, HL, Sweden

Site Status

Countries

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Armenia Sweden

Central Contacts

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Alexander G. Panossian, PhD

Role: CONTACT

+46733306226

Jennifer Hansgate

Role: CONTACT

Facility Contacts

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Samvel Hairumyan, PhD, MD

Role: primary

+37493203057

Areg Hovhannisyan, PhD Areg Hovhannisyan, PhD, PhD

Role: primary

+37494282018

Aghavni Ginosyan, PhD, MD

Role: primary

+37493360653

Alexander G.

Role: primary

+46733306226

References

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Liu CS, Zheng YR, Zhang YF, Long XY. Research progress on berberine with a special focus on its oral bioavailability. Fitoterapia. 2016 Mar;109:274-82. doi: 10.1016/j.fitote.2016.02.001. Epub 2016 Feb 2.

Reference Type BACKGROUND
PMID: 26851175 (View on PubMed)

Xu X, Yi H, Wu J, Kuang T, Zhang J, Li Q, Du H, Xu T, Jiang G, Fan G. Therapeutic effect of berberine on metabolic diseases: Both pharmacological data and clinical evidence. Biomed Pharmacother. 2021 Jan;133:110984. doi: 10.1016/j.biopha.2020.110984. Epub 2020 Nov 10.

Reference Type BACKGROUND
PMID: 33186794 (View on PubMed)

Loftsson T, Moya-Ortega MD, Alvarez-Lorenzo C, Concheiro A. Pharmacokinetics of cyclodextrins and drugs after oral and parenteral administration of drug/cyclodextrin complexes. J Pharm Pharmacol. 2016 May;68(5):544-55. doi: 10.1111/jphp.12427. Epub 2015 Jun 9.

Reference Type BACKGROUND
PMID: 26059798 (View on PubMed)

Kamigauchi M, Kawanishi K, Ohishi H, Ishida T. Inclusion effect and structural basis of cyclodextrins for increased extraction of medicinal alkaloids from natural medicines. Chem Pharm Bull (Tokyo). 2007 May;55(5):729-33. doi: 10.1248/cpb.55.729.

Reference Type BACKGROUND
PMID: 17473458 (View on PubMed)

Hopwood VL, Pathak S. Improved quality of Giemsa banding by the use of trypsin concentrate. Am Biotechnol Lab. 1994 Oct;12(11):52. No abstract available.

Reference Type BACKGROUND
PMID: 7765426 (View on PubMed)

Tannous M, Caldera F, Hoti G, Dianzani U, Cavalli R, Trotta F. Drug-Encapsulated Cyclodextrin Nanosponges. Methods Mol Biol. 2021;2207:247-283. doi: 10.1007/978-1-0716-0920-0_19.

Reference Type BACKGROUND
PMID: 33113141 (View on PubMed)

Uekama K. Design and evaluation of cyclodextrin-based drug formulation. Chem Pharm Bull (Tokyo). 2004 Aug;52(8):900-15. doi: 10.1248/cpb.52.900.

Reference Type BACKGROUND
PMID: 15304981 (View on PubMed)

Other Identifiers

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EP-1007

Identifier Type: -

Identifier Source: org_study_id

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