Vitamin D and Calcium HomeostasisEarly Phase 1NCT02019875
CYP3A4 Activity and Mineral Homeostasis
A Early Phase 1 study testing Rifampin, Clarithromycin and Grapefruit Juice in people with Vitamin D and Calcium Homeostasis, run by University of Washington at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Vitamin D and Calcium Homeostasis
- What is being tested?
- Rifampin, Clarithromycin and Grapefruit Juice
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 92 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2014to Dec 2020
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Modulating CYP3A4 Activity on Mineral Homeostasis
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.
Read the 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.
- Conditions
- Vitamin D and Calcium Homeostasis
- Being tested
- Rifampin, Clarithromycin, Grapefruit Juice, Placebo
- Keywords
- Vitamin D, CYP3A4, Calcium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RifampinDrug
Also called Rifadin
P450 inducer
ClarithromycinDrug
Also called Biaxin
CYP3A4 and Pgp inhibitor in both intestine and liiver
Grapefruit JuiceOther
CYP3A4 inhibitor in intestine
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| Water | Placebo comparator | 200 mL of water once a day for 14 days Receives: Other: Placebo |
| Rifampin | Active comparator | Rifampin 600 mg once a day for 14 days Receives: Drug: Rifampin |
| Grapefruit Juice | Active comparator | 200 mL of grapefruit juice once a day for 14 days Receives: Other: Grapefruit Juice |
| Grapefruit Juice Plus Rifampin | Active comparator | 200 mL of grapefruit juice once a day for 8 days plus rifampin 600 mg once a day for 14 days Receives: Drug: Rifampin; Other: Grapefruit Juice |
| Clarithromycin | Active comparator | Clarithromycin 250 mg twice a day for 14 days Receives: Drug: Clarithromycin |
| Clarithromycin Plus Rifampin | Active comparator | Clarithromycin 250 mg twice a day for 14 days plus rifampin 600 mg once a day for 14 days Receives: Drug: Rifampin; Drug: Clarithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
1, 25(OH) D3 Vitamin D
Serum 1, 25(OH) D3 Vitamin D
Measured: 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).
25(OH) D3 Vitamin D
Serum 25(OH) D3 Vitamin D
Measured: 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).
Parathyroid Hormone
Blood Parathyroid Hormone
Measured: 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).
Osteocalcin
Serum Osteocalcin
Measured: 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).
Calcium, Ionized
Serum
Measured: 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).
Calcium/Creatinine (mg/g)
Urine Calcium/Creatinine (mg/g)
Measured: 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).
Phosphate/Creatinine (mg/g)
Urine Phosphate/Creatinine(mg/g)
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2013 (estimated)
- Study startJun 2014
- Primary completionDec 2020
- Study completionDec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Vitamin D and Calcium HomeostasisStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Responsible party
- Principal investigator, Kenneth Thummel, University of Washington
- Investigators
- Kenneth Thummel, Ph.D., Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02019875
- Sponsor's protocol ID
- STUDY00001894
- Other IDs
- R01GM063666
- Status last verified
- Mar 2023
- First submitted
- 18 Dec 2013
- Last updated
- 19 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Modulating CYP3A4 Activity on Mineral Homeostasis
- ClinicalTrials.gov ID
- NCT02019875
- Acronym / sponsor ID
- STUDY00001894
- Conditions
- Vitamin D and Calcium Homeostasis
- Keywords
- Vitamin D, CYP3A4, Calcium
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Study start
- Jun 2014
- Primary completion
- Dec 2020 (actual)
- Study completion
- Dec 2020 (actual)
- First posted
- 24 Dec 2013 (estimated)
- Results
- Posted 19 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Water | Placebo comparator | Other: Placebo200 mL of water once a day for 14 days |
| Rifampin | Active comparator | Drug: RifampinRifampin 600 mg once a day for 14 days |
| Grapefruit Juice | Active comparator | Other: Grapefruit Juice200 mL of grapefruit juice once a day for 14 days |
| Grapefruit Juice Plus Rifampin | Active comparator | Drug: Rifampin, Other: Grapefruit Juice200 mL of grapefruit juice once a day for 8 days plus rifampin 600 mg once a day for 14 days |
| Clarithromycin | Active comparator | Drug: ClarithromycinClarithromycin 250 mg twice a day for 14 days |
| Clarithromycin Plus Rifampin | Active comparator | Drug: Rifampin, Drug: ClarithromycinClarithromycin 250 mg twice a day for 14 days plus rifampin 600 mg once a day for 14 days |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RifampinAlso: RifadinP450 inducer | Drug | Clarithromycin Plus Rifampin, Grapefruit Juice Plus Rifampin, Rifampin |
| ClarithromycinAlso: BiaxinCYP3A4 and Pgp inhibitor in both intestine and liiver | Drug | Clarithromycin, Clarithromycin Plus Rifampin |
| Grapefruit JuiceCYP3A4 inhibitor in intestine | Other | Grapefruit Juice, Grapefruit Juice Plus Rifampin |
| Placebo | Other | Water |
Primary outcome
1, 25(OH) D3 Vitamin D
Time frame: 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).
Serum 1, 25(OH) D3 Vitamin D
25(OH) D3 Vitamin D
Time frame: 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).
Serum 25(OH) D3 Vitamin D
Parathyroid Hormone
Time frame: 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).
Blood Parathyroid Hormone
Osteocalcin
Time frame: 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).
Serum Osteocalcin
Calcium, Ionized
Time frame: 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).
Serum
Calcium/Creatinine (mg/g)
Time frame: 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).
Urine Calcium/Creatinine (mg/g)
Phosphate/Creatinine (mg/g)
Time frame: 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).
Urine Phosphate/Creatinine(mg/g)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kenneth Thummel, Ph.D. principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Rifampin, Clarithromycin and Grapefruit Juice in people with Vitamin D and Calcium Homeostasis, run by University of Washington at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1, 25(OH) D3 Vitamin D (time frame: 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).). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2023.