HealthyNCT01173640
Resveratrol and Midazolam Metabolism
A study testing Midazolam, resveratrol (single dose) and resveratrol (multiple dose) in people with Healthy, run by University of Washington at 1 site in United States.
Trial summary
Adverse events due to drug-drug and/or herb-drug interactions are of serious concern and a major cause of morbidity and mortality. Resveratrol is a polyphenol antioxidant that has been identified in over 70 species and is suggested to be the constituent in red wine responsible for cardioprotective effects. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Midazolam, resveratrol (single dose) and resveratrol (multiple dose)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2010to Feb 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 18 to 50 years old.
- Body mass index between 18 and 30 kg/m2.
- Good health without a self-reported history of liver, kidney, gastrointestinal or heart disease
- Women use measures to avoid conception during the study period (e.g. oral contraceptives, intrauterine devices [IUDs], and condoms)
- Subjects must agree not to take any known substrates, inhibitors, inducers or activators of CYP3A4 at least 2 weeks before study start and for the entire duration of the study.
- Avoid ingesting grapefruit, grapefruit juice or other grapefruit juice containing products, and any herbal-based nutrient supplement or prescribed medications during the same period of time.
- Willing to fast overnight before the study days.
- Willing to abstain from alcohol-containing beverages 24 hours before and during the study visits, and willing to abstain from grapefruit, cranberry, blueberry products, peanuts and peanut butter, grape and grape products, and red wine at least one week prior to and during the study.
Who cannot join
- Current cigarette smoker
- Self-reported history of liver, kidney, gastrointestinal or heart disease
- Abnormal liver or kidney function tests based on the Comprehensive and Hepatic Panel (below the lower end or greater than 15% of the upper end of the reference range).
- Known or suspected history of alcohol or drug abuse
- Allergic to benzodiazepines or any other chemically related drugs
- Women who are pregnant or breastfeeding
Show all 10Show fewer
- Recent ingestion (<1 week) of any medication known to be metabolized by CYP3A4 or alter CYP3A activity
- Chronic use of prescription drugs, over-the-counter, vitamins or natural products. However, oral contraceptives will be permitted.
- Unable to give informed consent
- Participated in another clinical trial or study within 30 days
Trial locations and contacts
1 site in 1 country.
About this study
Adverse events due to drug-drug and/or herb-drug interactions are of serious concern and a major cause of morbidity and mortality. Resveratrol is a polyphenol antioxidant that has been identified in over 70 species and is suggested to be the constituent in red wine responsible for cardioprotective effects. The potential health benefits of resveratrol supplements are highly extolled in the alternative medicine industry and daily doses are up to 5 grams are being studied. While there are potential health benefits of high doses of resveratrol, for patients taking other drugs metabolized by CYP3A4, such as transplant medications, chemotherapies and HMG-CoA reductase inhibitors, there may be a clinically significant herb-drug interaction.
We, the investigators, have shown in vitro that resveratrol is a mechanism-based inhibitor of cytochrome P450 3A4 (CYP3A4). Based on our in vitro evidence and literature reports of the pharmacokinetics of resveratrol, we hypothesize that resveratrol will be a potent in vivo mechanism-based inhibitor of intestinal CYP3A4 enzymes. To date, there are no clinical studies that address the potential for a resveratrol-drug interaction. We propose to test whether single and multiple doses of resveratrol alter the pharmacokinetics of midazolam, a prototypic CYP3A4 probe drug.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MidazolamDrug
Also called Versed
2 mg oral dose
resveratrol (single dose)Dietary supplement
1 g oral dose
resveratrol (multiple dose)Dietary supplement
1 g oral dose for 8 days
| Study group | Role | What they receive |
|---|---|---|
| Midazolam Alone | Experimental | Baseline pharmacokinetics. On Study Visit Day 1, subjects will receive a single oral dose of midazolam (2 mg). Blood and urine will be collected to measure midazolam and its metabolites, and resveratrol and its metabolites. Receives: Drug: Midazolam |
| Single dose resveratrol | Experimental | On Study Visit Day 8, subjects will receive a 1 g oral dose of resveratrol followed 2 hours later by a single oral dose of midazolam (2 mg). Blood and urine will be collected to measure midazolam and its metabolites, and resveratrol and its metabolites. Receives: Drug: Midazolam; Dietary Supplement: resveratrol (single dose) |
| Multiple dose resveratrol | Experimental | Between Study Visit Days 8 and 15, subjects will take a 1 g dose of resveratrol daily. On Study Visit Day 15, subjects will receive a 1 g oral dose of resveratrol followed 2 hours later by a single oral dose of midazolam (2 mg). Blood and urine will be collected to measure midazolam and its metabolites, and resveratrol and its metabolites. Receives: Drug: Midazolam; Dietary Supplement: resveratrol (multiple dose) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Inhibition of midazolam clearance
The primary aim will be to determine if resveratrol causes inhibition of intestinal and hepatic CYP3A4 enzymes as determined by oral midazolam clearance following single and multiple doses of resveratrol, respectively.
Measured: 3 study visit days
Secondary outcomes (1)
Resveratrol accumulation
Secondary aims will be to measure circulating levels of resveratrol and its conjugated metabolites following single and multiple doses of resveratrol and to determine resveratrol accumulation in low density lipoproteins (LDL).
Measured: 3 study visit days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2010 (estimated)
- Study startJul 2010
- Primary completionFeb 2011
- Study completionFeb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies 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
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- Bastyr University
- Responsible party
- Principal investigator, Yvonne Lin, University of Washington
- Investigators
- Yvonne S Lin, PhD, Principal investigator, University of WashingtonRyan Bradley, ND, MPH, Principal investigator, Bastyr UniversityKelsey Hanson, MS, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01173640
- Sponsor's protocol ID
- 38328
- Status last verified
- Oct 2017
- First submitted
- 29 Jul 2010
- Last updated
- 31 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Resveratrol and Midazolam Metabolism
- ClinicalTrials.gov ID
- NCT01173640
- Acronym / sponsor ID
- 38328
- Conditions
- Healthy
- Keywords
- drug interactions, midazolam, cytochrome P450, resveratrol, pharmacokinetics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- Bastyr University
- Study start
- Jul 2010
- Primary completion
- Feb 2011 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 2 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Adverse events due to drug-drug and/or herb-drug interactions are of serious concern and a major cause of morbidity and mortality. Resveratrol is a polyphenol antioxidant that has been identified in over 70 species and is suggested to be the constituent in red wine responsible for cardioprotective effects. The potential health benefits of resveratrol supplements are highly extolled in the alternative medicine industry and daily doses are up to 5 grams are being studied. While there are potential health benefits of high doses of resveratrol, for patients taking other drugs metabolized by CYP3A4, such as transplant medications, chemotherapies and HMG-CoA reductase inhibitors, there may be a clinically significant herb-drug interaction.
We, the investigators, have shown in vitro that resveratrol is a mechanism-based inhibitor of cytochrome P450 3A4 (CYP3A4). Based on our in vitro evidence and literature reports of the pharmacokinetics of resveratrol, we hypothesize that resveratrol will be a potent in vivo mechanism-based inhibitor of intestinal CYP3A4 enzymes. To date, there are no clinical studies that address the potential for a resveratrol-drug interaction. We propose to test whether single and multiple doses of resveratrol alter the pharmacokinetics of midazolam, a prototypic CYP3A4 probe drug.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Midazolam Alone | Experimental | Drug: MidazolamBaseline pharmacokinetics. On Study Visit Day 1, subjects will receive a single oral dose of midazolam (2 mg). Blood and urine will be collected to measure midazolam and its metabolites, and resveratrol and its metabolites. |
| Single dose resveratrol | Experimental | Drug: Midazolam, Dietary Supplement: resveratrol (single dose)On Study Visit Day 8, subjects will receive a 1 g oral dose of resveratrol followed 2 hours later by a single oral dose of midazolam (2 mg). Blood and urine will be collected to measure midazolam and its metabolites, and resveratrol and its metabolites. |
| Multiple dose resveratrol | Experimental | Drug: Midazolam, Dietary Supplement: resveratrol (multiple dose)Between Study Visit Days 8 and 15, subjects will take a 1 g dose of resveratrol daily. On Study Visit Day 15, subjects will receive a 1 g oral dose of resveratrol followed 2 hours later by a single oral dose of midazolam (2 mg). Blood and urine will be collected to measure midazolam and its metabolites, and resveratrol and its metabolites. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 18 to 50 years old.
- Body mass index between 18 and 30 kg/m2.
- Good health without a self-reported history of liver, kidney, gastrointestinal or heart disease
- Women use measures to avoid conception during the study period (e.g. oral contraceptives, intrauterine devices [IUDs], and condoms)
- Subjects must agree not to take any known substrates, inhibitors, inducers or activators of CYP3A4 at least 2 weeks before study start and for the entire duration of the study.
Key exclusion criteria (10 listed)
- Current cigarette smoker
- Self-reported history of liver, kidney, gastrointestinal or heart disease
- Abnormal liver or kidney function tests based on the Comprehensive and Hepatic Panel (below the lower end or greater than 15% of the upper end of the reference range).
- Known or suspected history of alcohol or drug abuse
- Allergic to benzodiazepines or any other chemically related drugs
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 |
|---|---|---|
| MidazolamAlso: Versed2 mg oral dose | Drug | Midazolam Alone, Multiple dose resveratrol, Single dose resveratrol |
| resveratrol (single dose)1 g oral dose | Dietary supplement | Single dose resveratrol |
| resveratrol (multiple dose)1 g oral dose for 8 days | Dietary supplement | Multiple dose resveratrol |
Primary outcome
Inhibition of midazolam clearance
Time frame: 3 study visit days
The primary aim will be to determine if resveratrol causes inhibition of intestinal and hepatic CYP3A4 enzymes as determined by oral midazolam clearance following single and multiple doses of resveratrol, respectively.
1 secondary outcome
Resveratrol accumulation
Time frame: 3 study visit days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2017.
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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.
Yvonne S Lin, PhD principal investigator
University of Washington
Ryan Bradley, ND, MPH principal investigator
Bastyr University
Kelsey Hanson, MS 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 study testing Midazolam, resveratrol (single dose) and resveratrol (multiple dose) in people with Healthy, 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 8 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 31 Oct 2017. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Inhibition of midazolam clearance (time frame: 3 study visit days). 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 31 Oct 2017.