A Phase 1 interventional study of oral microencapsulated diindolylmethane in Healthy, no Evidence of Disease, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged 18 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-12-29.
Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Prevention
This randomized phase I trial is studying the side effects and best dose of diindolylmethane in healthy volunteers. Chemoprevention is the use of certain drugs or substances to keep cancer from forming, growing, or coming back. The use of diindolylmethane may keep cancer from forming. Collecting and storing samples of blood and urine from healthy volunteers to study in the laboratory may help doctors learn more about the way a person's body handles the drug.
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
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.
TERTIARY OBJECTIVES:
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.
National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.
Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.
Counted across the registry records on this site, refreshed daily.
Criteria:
Participants receive low-dose oral diindolylmethane (BR-DIM) twice daily for 4 weeks.
Drug: oral microencapsulated diindolylmethane
Participants receive high-dose oral BR-DIM twice daily for 4 weeks.
Drug: oral microencapsulated diindolylmethane
Given PO
Also known as: BioResponse DIM, BR-DIM
Effect of diindolylmethane (BR-DIM) on activities of CYP3A4 and CYP1A2
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.
Time frame: Up to 1 week
Grade 2 or higher toxicities, graded using NCI CTC version 2.0
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.
Time frame: Up to 1 week
Steady-state pharmacokinetic parameters such as half-life, Cmax, Tmax, and AUC
Pharmacokinetic parameters between pre- and post-menopausal women will be compared using the Wilcoxon rank-sum test.
Time frame: Up to 1 week
Drug metabolizing enzyme values (CYP2C9, CYP2D6, P-glycoprotein/OATP, and glutathione-S-transferase)
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.
Time frame: Up to 1 week
2/16 alpha OHE ratio in urine
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.
Time frame: Up to 1 month
This study is completed, as verified in Dec 2016. You cannot join it, but the record below documents what was studied.
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National Cancer Institute (NCI)