Interaction Between St John's Wort and Metformin?

Study Overview
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Brief Summary
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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.

Official Title
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Is There a Pharmacokinetic Interaction Between St John's Wort and Metformin?

Conditions
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Type 2 Diabetes, Depression

Intervention / Treatment
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* Other: St John's Wort
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br>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<br> <br> Drug: Metformin<br> <br> |

What is the study measuring?
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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) |