Interaction Between St John's Wort and Metformin?
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.
Type 2 Diabetes
Other: St John's Wort
|Study Design:||Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||Is There a Pharmacokinetic Interaction Between St John's Wort and Metformin?|
- Change 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
- 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
- Hypericin/hyperforin [ Time Frame: At t=0 in 2nd period ] [ Designated as safety issue: No ]If possible measure the concentrations of some of the active components of St John's Wort, hypericin and hyperforin
|Study Start Date:||January 2013|
|Study Completion Date:||May 2014|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
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
|Other: St John's Wort Drug: Metformin|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01726764
|Department of Clinical Pharmacology, Institute of Public Health, University of Southern Denmark|
|Odense, Denmark, DK-5000|
|Principal Investigator:||Per Damkier, MD ph.d.||University of Southern Denmark|
|Principal Investigator:||Tore B. Stage, M.Sc. Pharm||University of Southern Denmark|
|Study Director:||Kim Brøsen, Professor, MD||University of Southern Denmark|