Interaction Between St John's Wort and Metformin?

Is There a Pharmacokinetic 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.

Study Overview

• Status: Completed
• Conditions: Depression; Type 2 Diabetes
• Intervention / Treatment: Drug: Metformin; Other: St John's Wort

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 62 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Drug: Metformin; Other: St John's Wort

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oral glucose tolerance test (OGTT)	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.	During the first 2 hours of each metformin ingestion
Pharmacokinetics of metformin	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.	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
Change in messenger RiboNucleic Acid (mRNA)	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	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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypericin/hyperforin	If possible measure the concentrations of some of the active components of St John's Wort, hypericin and hyperforin	At t=0 in 2nd period

Collaborators and Investigators

• Sponsor: University of Southern Denmark
• Investigators: 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

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: November 2, 2012
• First Submitted That Met QC Criteria: November 9, 2012
• First Posted (Estimate): November 15, 2012

Study Record Updates

• Last Update Posted (Estimate): December 3, 2014
• Last Update Submitted That Met QC Criteria: December 2, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: AKF-382