Diindolylmethane in Healthy Volunteers

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

Healthy, no Evidence of Disease

Treatments

Drug: oral microencapsulated diindolylmethane

Study type

Interventional

Funder types

NIH

Identifiers

NCT00392652

NCI-2009-00867 (Registry Identifier)

N01CN35008 (Other Identifier)

CDR0000511393

HSC # 9139

N01-CN-35008-3 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

14 patients

Sex

All

Ages

18 to 70 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

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