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Interaction Between St John's Wort and Metformin?

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Tore B. Stage, University of Southern Denmark
ClinicalTrials.gov Identifier:
NCT01726764
First received: November 2, 2012
Last updated: November 1, 2013
Last verified: November 2013
  Purpose

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 Intervention Phase
Type 2 Diabetes
Depression
Other: St John's Wort
Drug: Metformin
Phase 1

Study Type: Interventional
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?

Resource links provided by NLM:


Further study details as provided by University of Southern Denmark:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Other Outcome Measures:
  • 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


Estimated Enrollment: 22
Study Start Date: January 2013
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01726764

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

No publications provided

Responsible Party: Tore B. Stage, M.Sc. Pharm, University of Southern Denmark
ClinicalTrials.gov Identifier: NCT01726764     History of Changes
Other Study ID Numbers: AKF-382
Study First Received: November 2, 2012
Last Updated: November 1, 2013
Health Authority: Denmark: Danish Health and Medicines Authority

Additional relevant MeSH terms:
Depression
Diabetes Mellitus, Type 2
Behavioral Symptoms
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Metformin
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014