Interaction Between St John's Wort and Metformin?

Phase 1

Completed

• Conditions: Depression; Type 2 Diabetes
• Interventions: Other: St John's Wort; Drug: Metformin

• Registration Number: NCT01726764
• Lead Sponsor: University of Southern Denmark

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 Description

Not available

Study Timeline

• Study First Submitted: 2012-11-02
• Study First Submitted QC: 2012-11-09
• Study First Posted: 2012-11-15
• Study Start: 2013-01
• Primary Completion: 2013-06
• Study Completion: 2014-05
• Status Verified: 2014-12
• Last Update Submitted: 2014-12-02
• Last Update Posted: 2014-12-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Metformin	St John's Wort	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
Metformin	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

Primary Outcome Measures

Name	Time	Method
Change in Area Under Curve (AUC) 0-24h of metformin	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	Change in 0-24h AUC of metformin after 3 weeks of treatment with St John's Wort

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics of metformin	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	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)	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)	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
Oral glucose tolerance test (OGTT)	During the first 2 hours of each metformin ingestion	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.

Trial Locations

Locations (1)

Department of Clinical Pharmacology, Institute of Public Health, University of Southern Denmark; 🇩🇰 Odense, Denmark