Trial Outcomes & Findings for Sulforaphane as an Antagonist to Human PXR-mediated Drug-drug Interactions (NCT NCT00621309)
NCT ID: NCT00621309
Last Updated: 2019-09-06
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
29 participants
Primary outcome timeframe
7 days
Results posted on
2019-09-06
Participant Flow
29 participants signed consent form. 23 participants had full measures for data analysis.
Participant milestones
| Measure |
Cross-over Trial -Sequence ABC
Three-armed, randomized, crossover trial, 7 days each arm. Arm A: 450 μmol SFN (Broccoli Sprout extract) and Rifampin, then Arm B: 450 μmol SFN (Broccoli Sprout extract), then Arm C: Placebo and Rifampin
|
Sequence ACB
Three-armed, randomized, crossover trial, 7 days each arm. Arm A: 450 μmol SFN (Broccoli Sprout extract) and Rifampin then Arm C: Placebo and Rifampin and then Arm B: 450 μmol SFN (Broccoli Sprout extract)
|
Sequence BAC
Three-armed, randomized, crossover trial, 7 days each arm. Arm B: 450 μmol SFN (Broccoli Sprout extract) then Arm A: 450 μmol SFN (Broccoli Sprout extract) and Rifampin and then Arm C: Placebo and Rifampin
|
Sequence BCA
Three-armed, randomized, crossover trial, 7 days each arm. Arm B: 450 μmol SFN (Broccoli Sprout extract), then Arm C: Placebo and Rifampin, and then Arm A: 450 μmol SFN (Broccoli Sprout extract) and Rifampin
|
Sequence CAB
Three-armed, randomized, crossover trial, 7 days each arm. Arm C: Placebo and Rifampin, then Arm A: 450 μmol SFN (Broccoli Sprout extract) and Rifampin and then Arm B: 450 μmol SFN (Broccoli Sprout extract)
|
Sequence CBA
Three-armed, randomized, crossover trial, 7 days each arm. Arm C: Placebo and Rifampin, then Arm B: 450 μmol SFN (Broccoli Sprout extract), and then Arm A: 450 μmol SFN (Broccoli Sprout extract) and Rifampin
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
4
|
5
|
6
|
4
|
4
|
|
Overall Study
COMPLETED
|
4
|
4
|
4
|
5
|
3
|
3
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
1
|
1
|
1
|
1
|
Reasons for withdrawal
| Measure |
Cross-over Trial -Sequence ABC
Three-armed, randomized, crossover trial, 7 days each arm. Arm A: 450 μmol SFN (Broccoli Sprout extract) and Rifampin, then Arm B: 450 μmol SFN (Broccoli Sprout extract), then Arm C: Placebo and Rifampin
|
Sequence ACB
Three-armed, randomized, crossover trial, 7 days each arm. Arm A: 450 μmol SFN (Broccoli Sprout extract) and Rifampin then Arm C: Placebo and Rifampin and then Arm B: 450 μmol SFN (Broccoli Sprout extract)
|
Sequence BAC
Three-armed, randomized, crossover trial, 7 days each arm. Arm B: 450 μmol SFN (Broccoli Sprout extract) then Arm A: 450 μmol SFN (Broccoli Sprout extract) and Rifampin and then Arm C: Placebo and Rifampin
|
Sequence BCA
Three-armed, randomized, crossover trial, 7 days each arm. Arm B: 450 μmol SFN (Broccoli Sprout extract), then Arm C: Placebo and Rifampin, and then Arm A: 450 μmol SFN (Broccoli Sprout extract) and Rifampin
|
Sequence CAB
Three-armed, randomized, crossover trial, 7 days each arm. Arm C: Placebo and Rifampin, then Arm A: 450 μmol SFN (Broccoli Sprout extract) and Rifampin and then Arm B: 450 μmol SFN (Broccoli Sprout extract)
|
Sequence CBA
Three-armed, randomized, crossover trial, 7 days each arm. Arm C: Placebo and Rifampin, then Arm B: 450 μmol SFN (Broccoli Sprout extract), and then Arm A: 450 μmol SFN (Broccoli Sprout extract) and Rifampin
|
|---|---|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
1
|
1
|
1
|
1
|
Baseline Characteristics
Sulforaphane as an Antagonist to Human PXR-mediated Drug-drug Interactions
Baseline characteristics by cohort
| Measure |
Cross-Over Trial
n=23 Participants
Crossover trial, three-armed, randomized. The PXR ligand rifampicin (300 mg/d)was given alone for 7 days in Arm 1, or in daily combination with 450 μmol SFN (Broccoli Sprout extract) in Arm 2; SFN was given alone in arm 3. 29 participants consented, analysis done on 23 who finished all arms.
|
|---|---|
|
Age, Continuous
|
23.7 years
STANDARD_DEVIATION 3.6 • n=39 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
23 Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=39 Participants
|
|
Race (NIH/OMB)
White
|
17 Participants
n=39 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
PRIMARY outcome
Timeframe: 7 daysOutcome measures
| Measure |
Rifampicin Alone
n=23 Participants
Subjects are given 300 mg / 7 days of rifampicin to induce CYP3A4. Midazolam clearance is measured on the 8th day. Rifampicin: Rifampicin, an antibiotic used to treat TB, is administered at a dose of 300 mg day x 7 days to induce CYP3A5.
|
Broccoli Sprout Extract Plus Rifampin
n=23 Participants
Sulforaphane (SFN), a natural product derived from broccoli sprouts, is utilized as a putative inhibitor of ligand (Rifampin) activation of the Pregnane X-receptor. In this arm, both SFN (putative inhibitor of ligand binding to PXR) and Rifampin (strong activating ligand of PXR) are given together.
sulforaphane plus rifampicin: Sulforaphane (SFN) is an isothiocyanate derived from the plant phytochemical, glucoraphinin. It appears to inhibit ligand binding to the ligand activated nuclear transcription factor, Pregnane X-Receptor (PXR). This arm tests the hypothesis that SFN can block ligand binding to the PXR, thereby inhibiting transcriptional activation of PXR-regulated genes. Sulforaphane is administered daily for 7 days as a broccoli sprout extract, at a dose rate of 75 mg (\~420 umoles)per day for 7 days. Rifampicin is also administered once per day at a dose rate of 300 mg/day for 7 days.
|
Broccoli Sprout Extract Alone
n=23 Participants
This arm involves the administration of Sulforaphane (SFN) alone, in the absence of the PXR ligand, rifampicin. The hypothesis is that SFN will have no effect on the expression of PXR-regulated genes. Alternatively, it is possible that SFN could inhibit as yet unidentified endogenous ligands to the PXR receptor, thereby causing down-regulations of genes regulated wholely or in part by PXR. SFN is administered as a broccoli sprout extract at a dose rate of 75 mg (\~420 umoles) per day for 7 days.
sulforaphane alone: Sulforaphane (SFN) is an isothiocyanate derived from the plant phytochemical, glucoraraphinin. It appears to inhibit ligand binding to the ligand activated nuclear transcription factor, Pregnane X-Receptor (PXR). This arm tests the hypothesis that SFN can block ligand binding to the PXR, thereby inhibiting transcriptional activation of PXR-regulated genes
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|---|---|---|---|
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Midazolam Clearance (Pharmacokinetic Measure of Cytochrome P450 3A4 Activity)
MDZ AUC Day 1
|
604 ng*min/ml
Standard Deviation 212
|
552 ng*min/ml
Standard Deviation 171
|
541 ng*min/ml
Standard Deviation 222
|
|
Midazolam Clearance (Pharmacokinetic Measure of Cytochrome P450 3A4 Activity)
MDZ AUC Day 8
|
156 ng*min/ml
Standard Deviation 72
|
135 ng*min/ml
Standard Deviation 70
|
558 ng*min/ml
Standard Deviation 134
|
Adverse Events
Cross-over Trial
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place