Cholesterol Metabolites as Markers for CYP3A Induction

Not Applicable

Completed

• Conditions: CYP3A4 Induction
• Interventions: Drug: Rifampicin treatment

• Registration Number: NCT01340456
• Lead Sponsor: Karolinska University Hospital

Brief Summary

The objectives of this study are:

* To investigate if the endogenous cholesterol metabolite, 4beta-OHcholesterol could be used as a marker for induction of cytochrome P450 (CYP) 3A4.

* To compare 4beta-OHcholesterol with midazolam as a marker for induction of CYP3A4.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-04-15
• Study First Submitted QC: 2011-04-20
• Study First Posted: 2011-04-22
• Status Verified: 2011-05
• Study Start: 2011-05
• Primary Completion: 2011-07
• Study Completion: 2011-07
• Last Update Submitted: 2011-07-08
• Last Update Posted: 2011-07-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Females and males.
2. Age of 18 and above.
3. Caucasians.
4. Healthy as assessed by medical history and examination by principal investigator or delegated personnel.
5. Accept to refrain from herbal drugs, natural preparations, and grapefruit juice 48 hours before and during the study period.
6. Accept to completely refrain from alcohol during day -1 to 1 and R14-R16. During the rest of the study moderate alcohol use is permitted (equal to 1 glass of wine or 1 beer per day).
7. Women of childbearing age should accept using a reliable barrier contraceptive method throughout the study.
8. Women of childbearing age should have a negative pregnancy test at the screening visit.
9. Capable of following given instructions.
10. Has given written informed consent after receiving both oral and written study information.

Exclusion Criteria

1. Predisposal to allergic drug reactions.
2. Anamnestic and/or visual signs of infection.
3. Women are not allowed to use oral hormone-based contraceptives 2 weeks before start of study and during the study.
4. Participation in another study within one month before entering the present study.
5. Intake of any other drug that can influence the enzyme activity of CYP3A4.
6. Pregnancy.
7. Breast-feeding.
8. A history of liver disease.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Rifampicin 20 mg QD	Rifampicin treatment	-
Rifampicin 10 mg QD	Rifampicin treatment	-
Rifampicin 100 mg QD	Rifampicin treatment	-

Primary Outcome Measures

Name	Time	Method
Change in 4beta-OHcholesterol	Directly before treatment with rifampicin and 14 days after the end of treatment with rifampicin	The primary objective of the study is to investigate whether the endogenous cholesterol metabolite 4β-hydroxycholesterol could be used as a marker for induction of CYP3A4. For this purpose the induction of 4β-hydroxycholesterol formation will be compared to the induction of quinine and midazolam metabolism.

Secondary Outcome Measures

Name	Time	Method
Ratio between midazolam AUC induced and midazolam AUC uninduced	Before treatment with rifampicin and after 14 days of treatment with rifampicin	Secondary aim of the study is to compare 4β-hydroxycholesterol as a biomarker for CYP3A4 compared to 6β-hydroxycortisol/cortisol ratio, which sometimes is used as a marker for CYP3A4 induction.; Another secondary aim is to relate our estimations of CYP3A4-expression to measured levels of 25-OH-vitamin D.

Trial Locations

Locations (1)

Clinical Pharmacology Trial Unit (CPTU), Karolinska University Hospital; 🇸🇪 Stockholm, Sweden