Clinical trial NCT02019875: CYP3A4 Activity and Mineral Homeostasis
Official title: Effect of Modulating CYP3A4 Activity on Mineral Homeostasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Vitamin D and Calcium Homeostasis
Keywords: Vitamin D
CYP3A4
Calcium
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Institute of General Medical Sciences (NIGMS)
First posted: 2013-12-24
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to determine whether changes in the activity of the enzyme CYP3A4 can change the Vitamin D and bone mineral homeostasis.

Detailed description: Healthy volunteers will receive one of six interventions for 14 days (determined by randomization):a). 200 mL of water once a day; b) rifampin 600 mg once a day; c) 200 mL of grapefruit juice once a day for 8 days plus rifampin 600 mg once a day for 14 days; d) clarithromycin 250 mg twice a day; f) clarithromycin 250 mg twice a day plus rifampin 600 mg once a day.

Eligibility criteria: Inclusion Criteria:

* Subjects with no history of significant medical conditions including cardiac, pulmonary, gastrointestinal, or renal disease, HIV, diabetes mellitus or Hepatitis B or C
* Subjects will be males or females 18-60 years of age
* Subjects must read and understand English
* Subjects must be able to provide informed consent
* Subjects must be willing to avoid prescription medications, OTC drugs, dietary supplements and foods that are known to modulate CYP3A4 expression or activity
* Subjects must be willing to maintain a consistent consumption of calcium and Vitamin D during the study and maintain a daily logbook of their dietary consumption
* Women not currently pregnant or lactating. In addition, women participants of childbearing age must be willing to utilize a barrier method of birth control (sterilization will be acceptable)
* Subjects will have no known allergies to the study drugs to be used
* Subject's corrected QTc interval obtained by electrocardiogram will be ≤ 430 ms in men or ≤ 450 ms in women

Exclusion Criteria:

* Subjects with any significant chronic medical condition, including cardiac, pulmonary, gastrointestinal, or renal disease, HIV, diabetes mellitus or Hepatitis B or C
* Subjects less than 18 or greater than 60 years of age
* Subjects unable to read and understand English
* Subjects unable to provide informed consent
* Subjects unable to avoid prescription medications, OTC drugs, dietary supplements and foods that are known to modulate CYP3A4 expression or activity
* Subjects not willing to maintain a consistent consumption of calcium and Vitamin D during the study and maintain a daily logbook of their dietary consumption
* Women who are pregnant or lactating and women participants of childbearing age not willing to utilize a barrier method of birth control (sterilization will be acceptable)
* Subjects with allergies to rifampin, clarithromycin or grapefruit juice
* Potential participants will be excluded if they are concurrently participating in another research study
* Subjects with corrected QTc interval \> 430 ms in men or \> 450 ms in women on electrocardiogram

Primary outcomes:
measure: 1, 25(OH) D3 Vitamin D
timeFrame: Samples will be collected on days 1, 4 and 7, and day 22 (last day of intervention). Treatment began on day 8. Data presented is day 22 concentration - Baseline (the average of day 1, day 4 and day 7 concentrations).
measure: 25(OH) D3 Vitamin D
timeFrame: Samples will be collected on days 1, 4 and 7, and day 22 (last day of intervention). Treatment began on day 8. Data presented is day 22 concentration - Baseline (the average of day 1, day 4 and day 7 concentrations).
measure: Parathyroid Hormone
timeFrame: Samples will be collected on days 1, 4 and 7, and day 22 (last day of intervention). Treatment began on day 8. Data presented is day 22 concentration - Baseline (the average of day 1, day 4 and day 7 concentrations).
measure: Osteocalcin
timeFrame: Samples will be collected on days 1, 4 and 7, and day 22 (last day of intervention). Treatment began on day 8. Data presented is day 22 concentration - Baseline (the average of day 1, day 4 and day 7 concentrations).
measure: Calcium, Ionized
timeFrame: Samples will be collected on days 1, 4 and 7, and day 22 (last day of intervention). Treatment began on day 8. Data presented is day 22 concentration - Baseline (the average of day 1, day 4 and day 7 concentrations).
measure: Calcium/Creatinine (mg/g)
timeFrame: Samples will be collected on days 1, 4 and 7, and day 22 (last day of intervention). Treatment began on day 8. Data presented is day 22 concentration - Baseline (the average of day 1, day 4 and day 7 concentrations).
measure: Phosphate/Creatinine (mg/g)
timeFrame: Samples will be collected on days 1, 4 and 7, and day 22 (last day of intervention). Treatment began on day 8. Data presented is day 22 concentration - Baseline (the average of day 1, day 4 and day 7 concentrations).
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Washington
name: Kenneth Thummel, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: