Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Diindolylmethane in Healthy Nonsmokers

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Biomarker/Laboratory analysis, Prevention	Closed	18 to 70	NCI	KUMC-HSC-9139 HSC# 9139, N01-CN-35008-1, NCT00784394

Objectives

Primary

1. To determine single oral doses of microencapsulated diindolylmethane (DIM) that are safe and well-tolerated in healthy volunteers.
2. To determine the pharmacokinetics of DIM in these participants.
3. To determine the effect of multiple daily dosing with DIM on the disposition of probe drugs metabolized by cytochrome P4501A2 (CYP1A2) and CYP3A4 in these participants.

Secondary

1. To determine the effect of multiple daily doses of DIM on estrogen metabolites in urine, and on activities of CYP2C9, CYP2D6, and P-glycoprotein (P-gp)/OATP (Organic Anion Transport Protein) in these participants.
2. To determine the effect of a single dose of DIM on the disposition of probe drugs that are metabolized or transported by CYP1A2, CYP2C9, CYP2D6, CYP3A4, and P-gp in these participants.
3. To determine the safety and tolerability of single and multiple daily doses of DIM.
4. To determine the pharmacokinetics of a single dose of DIM and of the same dose after chronic daily dosing.

Tertiary

1. To determine effects of DIM on activities of glutathione-S-transferase (GST) and quinone reductase (NQO1), and phase 2 enzymes in lymphocytes.
2. To determine effects of multiple daily doses of DIM on markers of susceptibility to cancer, including serum insulin-like growth factor-1 (IGF-1), and serum IGF-binding protein-3 (IGFBP-3).
3. To determine effects of multiple daily doses of DIM on selected markers of sexual function: estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone binding globulin (SHBG), and basal body temperature in women and testosterone, LH, and SHBG in men.

Entry Criteria

Disease Characteristics:

• Healthy, non-smoking volunteers
  • Non-smoker status confirmed by urine cotinine assay at baseline (Accutest NicoMeter Urine Professional strip or equivalent test)

Prior/Concurrent Therapy:

• No prior chemotherapy
• No investigational drug within the past three months
• At least 14 days since prior and no more than 3 concurrent medium servings (½ cup each) of cruciferous vegetable (i.e., broccoli, cabbage [including coleslaw], cauliflower, bok-choy, brussels sprouts, collards, kale, kohlrabi, mustard greens, rutabaga, turnip, and watercress) per week
• At least 7 days since prior and no concurrent alcohol intake
• No caffeine and grapefruit-containing foods and beverages for at least 48 hours before dosing
• No regular concomitant medications, herbal products, dietary supplements or high dose vitamins over the past 21 days
• No concurrent medications other than oral contraceptives or hormones

Patient Characteristics:

• Life expectancy ≥ 12 months
• Hemoglobin > 10 g/dL
• Absolute Granulocyte Count > 1,500/μL
• 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
• Not pregnant or nursing
• Negative pregnancy test
• Within +/- 20% of ideal body weight by the Metropolitan Life tables
• Strict vegetarians are excluded
• No serious drug allergies or other serious intolerance or allergies (mild seasonal allergies are allowed)
• No chronic headaches, dysphoria, fatigue, dizziness, blurred vision, insomnia, rhinorrhea, nausea, vomiting, abdominal pain, diarrhea, constipation, or similar conditions
• No serious acute or chronic illness (diabetes, arthritis, asthma, etc.) requiring chronic drug therapy
• No active malignancy

Expected Enrollment

Outcomes

Safety and toxicity of oral microencapsulated diindolylmethane (DIM) as assessed by NCI CTC v2.0
Maximum-tolerated dose of DIM
Pharmacokinetics of DIM

Outline

This is a dose-escalation, placebo-controlled study of oral microencapsulated diindolylmethane (DIM).

Participants receive a single dose of oral DIM daily for 6 days provided there is no unacceptable toxicity. In each dosing cohort, 1 participant is randomized to receive the matching placebo and 3 patients receive DIM.

Blood and urine are collected before administering DIM and serially during the following 24 hours for pharmacokinetic studies. Plasma is analyzed by liquid chromatography/mass spectroscopy and urine by gas chromatography/mass spectroscopy.

After completion of the study, participants are followed periodically for 3 months.

Trial Contact Information

Trial Lead Organizations

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

Aryeh Hurwitz, MD, Principal investigator		Ph: 913-588-6060

Registry Information
Official Title		Phase I Ascending Single Dose Pharmacokinetics (PK) and Safety Study of 3,3' Di-indolylmethane (DIM)
Trial Start Date		2004-04-02
Registered in ClinicalTrials.gov		NCT00784394
Date Submitted to PDQ		2008-10-14
Information Last Verified		2008-10-29
NCI Grant/Contract Number		CN-35008-38