Interaction Between St John's Wort and Metformin?

Overview[ - collapse ][ - ]

Purpose The goal of the study is to examine the difference of the pharmacokinetics of metformin with and without a 3 weeks pretreatment of St John's Wort. Furthermore secondary objectives include changes in GLP-1, C-peptide, serum-insulin and plasma-glucose during an oral glucose tolerance test, changes in OCT1 mRNA in plasma and changes in leptin and lipid-profile following this possible interaction.
ConditionType 2 Diabetes
Depression
InterventionOther: St John's Wort
Drug: Metformin
PhasePhase 1
SponsorUniversity of Southern Denmark
Responsible PartyUniversity of Southern Denmark
ClinicalTrials.gov IdentifierNCT01726764
First ReceivedNovember 2, 2012
Last UpdatedNovember 1, 2013
Last verifiedNovember 2013

Tracking Information[ + expand ][ + ]

First Received DateNovember 2, 2012
Last Updated DateNovember 1, 2013
Start DateJanuary 2013
Estimated Primary Completion DateDecember 2013
Current Primary Outcome MeasuresChange in Area Under Curve (AUC) 0-24h of metformin [Time Frame: Concentration of metformin at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24 hours after metformin ingestion] [Designated as safety issue: No]Change in 0-24h AUC of metformin after 3 weeks of treatment with St John's Wort
Current Secondary Outcome Measures
  • Oral glucose tolerance test (OGTT) [Time Frame: During the first 2 hours of each metformin ingestion] [Designated as safety issue: No]Changes in: Plasma-glucose, serum-insulin, glucagon-like peptide 1 (GLP-1) and connecting-peptides (C-peptides) during the oral glucose tolerance test, measured at 0, 0.5, 1, 1.5 and 2 hours after metformin ingestion.
  • Pharmacokinetics of metformin [Time Frame: Concentration of metformin at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24 hours after metformin ingestion, which will be used to determine the pharmacokinetic parameters mentioned below] [Designated as safety issue: No]Determination of other pharmacokinetic parameters of metformin such as clearance (CL), absorption fraction (F), distribution volume (V), the minimum concentration at steady state (Css,min), elimination half life (T 1/2) etc.
  • Change in messenger RiboNucleic Acid (mRNA) [Time Frame: Will be measured 4 times: At inclusion (t=0 on that day), at t=0 in both periods and minimum 3 weeks after finalization of the study (t=0 on that day)] [Designated as safety issue: No]Changes in mRNA encoding OCT1 will be measured at 4 different time points to give an insight to the importance of St John's Wort effect on the OCT1 production

Descriptive Information[ + expand ][ + ]

Brief TitleInteraction Between St John's Wort and Metformin?
Official TitleIs There a Pharmacokinetic Interaction Between St John's Wort and Metformin?
Brief Summary
The goal of the study is to examine the difference of the pharmacokinetics of metformin with
and without a 3 weeks pretreatment of St John's Wort. Furthermore secondary objectives
include changes in GLP-1, C-peptide, serum-insulin and plasma-glucose during an oral glucose
tolerance test, changes in OCT1 mRNA in plasma and changes in leptin and lipid-profile
following this possible interaction.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 1
Study DesignEndpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label
Condition
  • Type 2 Diabetes
  • Depression
InterventionOther: St John's Wort
Drug: Metformin
Study Arm (s)Experimental: Metformin
7 days of pretreatment with metformin before full pharmacokinetics and other goals are investigated.
Minimum 1 week of washout after this period. 3 weeks of pretreatment with St John's Wort and the last 7 days metformin is ingested again, and the same effect parameters as described above is performed again

Recruitment Information[ + expand ][ + ]

Recruitment StatusActive, not recruiting
Estimated Enrollment22
Estimated Completion DateDecember 2013
Estimated Primary Completion DateNovember 2013
Eligibility Criteria
Inclusion Criteria:

- Men aged 18-64 years

- Homozygous for common genetic variants in the genes organic cation transporter 1/2
(OCT1/OCT2)

- Normal values of biomarkers accounting for: Liver and kidney function, and normal
blood glucose

Exclusion Criteria:

- Chronic alcohol abuse

- Hypersensitivity to metformin or St John's Wort

- Daily intake of drugs requiring prescription
GenderMale
Ages18 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
ContactsNot Provided
Location CountriesDenmark

Administrative Information[ + expand ][ + ]

NCT Number NCT01726764
Other Study ID NumbersAKF-382
Has Data Monitoring CommitteeNo
Information Provided ByUniversity of Southern Denmark
Study SponsorUniversity of Southern Denmark
CollaboratorsNot Provided
Investigators Principal Investigator: Per Damkier, MD ph.d. University of Southern DenmarkPrincipal Investigator: Tore B. Stage, M.Sc. Pharm University of Southern DenmarkStudy Director: Kim Brøsen, Professor, MD University of Southern Denmark
Verification DateNovember 2013

Locations[ + expand ][ + ]

Department of Clinical Pharmacology, Institute of Public Health, University of Southern Denmark
Odense, Denmark, DK-5000