Ignite Creation Date:
2024-05-05 @ 7:12 PM
Last Modification Date:
2024-10-26 @ 9:45 AM
Study NCT ID:
NCT00621309
Status:
COMPLETED
Last Update Posted:
2019-09-06
First Post:
2008-02-12
Brief Title:
Sulforaphane as an Antagonist to Human PXR-mediated Drug-drug Interactions
Sponsor:
University of Washington
Organization:
University of Washington
Study Overview
Official Title:
Phase I Clinical Trial to Evaluate the Efficacy of Sulforaphane as an Antagonist to Human PXR-mediated Drug-drug Interactions
Status:
COMPLETED
Status Verified Date:
2019-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Adverse drug-drug interactions DDIs are responsible for approximately 3 of all hospitalizations in the US perhaps costing more than 13 billion per year One of the most common causes of DDIs is the when one drug alters the metabolism of another A key enzyme in the liver and intestine called cytochrome P450 3A4 CYP3A4 is generally considered to be the most important drug metabolizing enzyme The gene for CYP3A4 can be turned on by the presence of certain other drugs resulting in much higher levels of CYP3A4 in the liver and intestine Thus when a drug that induces CYP3A4 is given with or before another drug that is metabolized by 3A4 a drug-drug interaction occurs because the first drug the inducer greatly changes the rate at which the second drug CYP3A4 substrate is removed from the body Many drugs increase CYP3A4 activity by binding to a receptor called the Pregnane-X-Receptor PXR which is a major switch that controls the expression of the CYP3A4 gene Using human liver cells we have demonstrated that sulforaphane SFN found in broccoli can block drugs from activating the PXR receptor thereby inhibiting the switch that causes CYP3A4 induction The purpose of this project is to determine if SFN can be used to block adverse DDIs that occur when drugs bind to and activate the PXR receptor and subsequently induce CYP3A4 activity We will recruit 24 human volunteers to participate in the study This project will determine whether SFN can prevent the drug Rifampin from binding to PXR and increasing CYP3A4 activity in humans following oral administration of SFN broccoli sprout extract The rate of removal of a small dose of the drug midazolam will be used to determine the enzymatic activity of CYP3A4 before and following treatment with Rifampin in the presence or absence of SFN since midazolam is only eliminated from the bloodstream by CYP3A4 We predict that SFN will prevent the increase in midazolam clearance metabolism that normally follows treatment with the antibiotic rifampicin
This research is important because it could potentially lead to a simple cost-effective way of preventing one of the most common causes of adverse drug-drug interactions that occurs today For example rifampicin which is a cheap and effective antibiotic used to treat TB cannot be used in HIVAIDS patients because it increases the metabolism of many of the antiretroviral drugs used to treat HIVAIDS TB is a major opportunistic infection in AIDS patients so this is a serious clinical problem especially in developing countries where more expensive alternative drug therapies are not available We hypothesize that co-formulation of rifampicin with SFN could block this drug-drug interaction without altering its efficacy thereby allowing its use in HIVAIDS patients infected with TB This is but one example of numerous drug-drug interactions that occur via this mechanism
This research is important because it could potentially lead to a simple cost-effective way of preventing one of the most common causes of adverse drug-drug interactions that occurs today For example rifampicin which is a cheap and effective antibiotic used to treat TB cannot be used in HIVAIDS patients because it increases the metabolism of many of the antiretroviral drugs used to treat HIVAIDS TB is a major opportunistic infection in AIDS patients so this is a serious clinical problem especially in developing countries where more expensive alternative drug therapies are not available We hypothesize that co-formulation of rifampicin with SFN could block this drug-drug interaction without altering its efficacy thereby allowing its use in HIVAIDS patients infected with TB This is but one example of numerous drug-drug interactions that occur via this mechanism
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NIH grant 1R01GM079280-01A1 | None | None | None |
| 07-9114-A01 | None | None | None |