Interaction Between St John's Wort and Metformin?

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01726764
Recruitment Status : Completed
First Posted : November 15, 2012
Last Update Posted : December 3, 2014
Information provided by (Responsible Party):
Tore B. Stage, 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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Depression Other: St John's Wort Drug: Metformin Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Official Title: Is There a Pharmacokinetic Interaction Between St John's Wort and Metformin?
Study Start Date : January 2013
Actual Primary Completion Date : June 2013
Actual Study Completion Date : May 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions
U.S. FDA Resources

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

Other: St John's Wort Drug: Metformin

Primary Outcome Measures :
  1. 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 ]
    Change in 0-24h AUC of metformin after 3 weeks of treatment with St John's Wort

Secondary Outcome Measures :
  1. Oral glucose tolerance test (OGTT) [ Time Frame: 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.

  2. 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 ]
    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.

  3. 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) ]
    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

Other Outcome Measures:
  1. Hypericin/hyperforin [ Time Frame: At t=0 in 2nd period ]
    If possible measure the concentrations of some of the active components of St John's Wort, hypericin and hyperforin

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01726764

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

Responsible Party: Tore B. Stage, M.Sc. Pharm, University of Southern Denmark Identifier: NCT01726764     History of Changes
Other Study ID Numbers: AKF-382
First Posted: November 15, 2012    Key Record Dates
Last Update Posted: December 3, 2014
Last Verified: December 2014

Additional relevant MeSH terms:
Hypoglycemic Agents
Physiological Effects of Drugs