Diindolylmethane in Healthy Volunteers
Diindolylmethane in Healthy Volunteers
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.
Criteria:

 -  Healthy men and women

 -  Nonsmoker confirmed by urine cotinine test

 -  No active malignancy

 -  Life expectancy >= 12 months

 -  Hemoglobin > 10 g/dL

 -  Absolute granulocyte count > 1,500/mm^3

 -  Creatinine < 2.0 mg/dL

 -  Albumin > 3.0 g/dL

 -  Bilirubin < 1.8 mg/dL

 -  AST and ALT < 110 U/L

 -  Alkaline phosphatase < 300 U/L

 -  Body mass index =< 30

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile participants must use effective nonhormonal contraception

 -  No acute, unstable, chronic, or recurring medical conditions

 -  No strict vegetarians or consumption of > 3 medium servings (1/2 cup each) of
 cruciferous vegetables per week

 -  Participants who have stopped eating cruciferous vegetables within the past 2 weeks
 and agree to refrain from eating them for the duration of the study are eligible

 -  Cruciferous vegetables include broccoli, cabbage (including coleslaw), cauliflower,
 bok-choy, brussels sprouts, collards, kale, kohlrabi, mustard greens, rutabaga,
 turnip, and watercress

 -  No serious drug allergies or other serious intolerance or allergies

 -  Mild seasonal allergies allowed

 -  No chronic conditions, including headaches, dysphoria, fatigue, dizziness, blurred
 vision, insomnia, rhinorrhea, nausea, vomiting, abdominal pain, diarrhea,
 constipation, menopausal hot flashes/night sweats, or clinically significant
 premenstrual syndrome

 -  No serious acute or chronic illness

 -  No requirement for chronic drug therapy

 -  No alcohol ingestion within 48 hours of study treatment

 -  No investigational drugs within the past 3 months

 -  No prior chemotherapy

 -  No concurrent regular medications or hormones

 -  No recent change in medications or dosage of medications

 -  No concurrent regular supplements or vitamins

 -  No concurrent over-the-counter medications

 -  No concurrent grapefruit or its juice