Diindolylmethane in Healthy Volunteers
|ClinicalTrials.gov Identifier: NCT00392652|
Recruitment Status : Completed
First Posted : October 26, 2006
Last Update Posted : December 29, 2016
|Condition or disease||Intervention/treatment||Phase|
|Healthy, no Evidence of Disease||Drug: oral microencapsulated diindolylmethane||Phase 1|
I. Determine the effect of multiple daily dosing with nutritional-grade, absorption-enhanced diindolylmethane (BR-DIM) on the disposition of probe drugs metabolized by cytochrome P4501A2 (CYP1A2) and CYP3A4 in healthy volunteers.
I. Determine the effect of multiple daily doses of BR-DIM on estrogen metabolites in urine and on activities of CYP2C9, CYP2D6, and P-glycoprotein/OATP.
II. Determine the effect of a single dose of BR-DIM on the disposition of probe drugs that are metabolized or transported by CYP1A2, CYP2C9, CYP2D6, CYP3A4, and P-glycoprotein (P-go).
III. Determine the safety and tolerability of single and multiple daily doses of BR-DIM.
IV. Determine the pharmacokinetics of a single dose of BR-DIM and of the same dose after chronic daily dosing.
V. Determine the pharmacokinetics of a single dose of BR-DIM and of the same dose after chronic daily dosing.
I. To determine effects of BR-DIM on activities of glutathione-S-transferase (GST), a phase 2 enzyme, in lymphocytes.
OUTLINE: This is a randomized, double-blind study. Participants are stratified according to gender. Participants are randomized to 1 of 2 intervention arms.
Arm I: Participants receive low-dose oral diindolylmethane (BR-DIM) twice daily for 4 weeks.
Arm II: Participants receive high-dose oral BR-DIM twice daily for 4 weeks.
In both arms, participants receive an oral probe-drug cocktail comprising caffeine (CYP1A2), dextromethorphan (CYP2D6), buspirone (CYP3A4), losartan (CYP2C9), and fexofenadine (P-glycoprotein) before randomization and after the first and last dose of BR-DIM.
Blood and urine are collected periodically for pharmacokinetic profiles of BR-DIM and probe drugs.
After completion of study intervention, participants are followed at 1 week.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Phase 1 Multiple-Dose Safety, Pharmacokinetic, and Drug Interaction Clinical Study of Nutritional-Grade, Absorption-Enhanced DIM (BR-DIM)|
|Study Start Date :||November 2006|
|Actual Primary Completion Date :||October 2008|
|Actual Study Completion Date :||October 2009|
Experimental: Arm I (low-dose oral diindolylmethane)
Participants receive low-dose oral diindolylmethane (BR-DIM) twice daily for 4 weeks.
Drug: oral microencapsulated diindolylmethane
Experimental: Arm II (high-dose oral diinolylmethane)
Participants receive high-dose oral BR-DIM twice daily for 4 weeks.
Drug: oral microencapsulated diindolylmethane
- Effect of diindolylmethane (BR-DIM) on activities of CYP3A4 and CYP1A2 [ Time Frame: Up to 1 week ]Descriptive statistics will be calculated on all variables of interest: frequencies and percentages will be used to summarize categorical variables and medians, and ranges will summarize quantitative variables. Paired t-tests will be used to compare enzyme levels post-pre at each dose. Analysis of covariance will be used to determine if there is a dose effect on enzyme levels, using the baseline values as a covariate. If there is no dose effect, the seven subjects at each dose will be pooled which will provide an increase power to detect meaningful changes in enzyme levels.
- Grade 2 or higher toxicities, graded using NCI CTC version 2.0 [ Time Frame: Up to 1 week ]A one-sided binomial test will be used. Descriptive statistics will be calculated on all variables of interest: frequencies and percentages will be used to summarize categorical variables and medians, and ranges will summarize quantitative variables.
- Steady-state pharmacokinetic parameters such as half-life, Cmax, Tmax, and AUC [ Time Frame: Up to 1 week ]Pharmacokinetic parameters between pre- and post-menopausal women will be compared using the Wilcoxon rank-sum test.
- Drug metabolizing enzyme values (CYP2C9, CYP2D6, P-glycoprotein/OATP, and glutathione-S-transferase) [ Time Frame: Up to 1 week ]The probe drug values for the first three enzymes for the baseline (placebo) values and the first-dose BR-DIM values compared to assess inhibitory possible interactions, and between baseline and last-dose BR-DIM values to assess the possibility of either inhibitory or inductive events. Measurements of lymphocyte cytosolic GST activities will compare baseline to last-dose BR-DIM values, and thus assess the possibility of either inhibitory or inductive events. Since we anticipate skewed data, we will compare the values listed above using nonparametric Wilcoxon sign rank tests.
- 2/16 alpha OHE ratio in urine [ Time Frame: Up to 1 month ]A one-way repeated measures analysis of variance will be used to compare this ratio across treatment periods (baseline, one month on BR-DIM, one month after stopping BR-DIM). We will summarize 2/16 alpha OHE ratio at each dose by means and standard deviations. If there is a large degree of skewness the median and range will be utilized as summary measures and Friedman's test utilized to assess the effect of BR-DIM on metabolites of estrogen in urine.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00392652
|United States, Kansas|
|University of Kansas Medical Center|
|Kansas City, Kansas, United States, 66160|
|Principal Investigator:||Reed Greg||University of Kansas Medical Center|