Diindolylmethane in Preventing Cancer in Healthy Volunteers

Phase I Ascending Single Dose Pharmacokinetics (PK) and Safety Study of 3,3' Di-indolylmethane (DIM)

This phase I clinical trial studies the side effects and best dose of diindolylmethane in preventing cancer in healthy volunteers. Diindolylmethane is formed in the stomachs of people who eat a chemical that is normally found in vegetables, including cabbage, broccoli, Brussels sprouts, cauliflower, and watercress. Diindolylmethane may prevent the development of cancer.

PRIMARY OBJECTIVES:

I. To determine single oral doses of 3,3' di-indolylmethane (DIM) (diindolylmethane) that are safe and well- tolerated.

II. To determine the pharmacokinetics of these single oral doses of DIM.

OUTLINE: This is a dose-escalation study. Participants are randomized to 1 of 2 treatment arms.

ARM I: Participants receive a single dose of diindolylmethane orally (PO) on day 1.

ARM II: Participants receive a single dose of placebo orally (PO) on day 1.

After completion of study treatment, participants are followed up on days 2, 3, and 6.

Inclusion Criteria:

• Non-smokers and non-users of abuse drugs as confirmed by urine cotinine (Accutest NicoMeter Urine Professional strip or equivalent test) and drug screen at visit 1
• Free of acute, unstable, chronic or recurring medical conditions based on history, physical examination, laboratory tests; the laboratory tests to be performed will be: blood serum chemistry screen to include comprehensive metabolic panel (glucose, creatinine, urea nitrogen [blood urea nitrogen (BUN)], sodium, potassium, chloride, calcium, total bilirubin, protein, albumin, globulin, cholesterol and the enzymes alkaline phosphatase, aspartate aminotransferase [AST], and alanine aminotransferase [ALT]) and lipid panel (total, low density lipoprotein [LDL] and high density lipoprotein [HDL] cholesterol and triglycerides); complete blood count including differential and platelet count; prothrombin time; and routine urinalysis; values for laboratory tests must be within the ranges below grade 2 of Common Toxicity Criteria (CTC) and/or as specified below:
• Hemoglobin > 10 g/dL
• Absolute granulocyte count > 1500/ìL
• Creatinine < 2.0 mg/dl
• Albumin > 3.0 g/dl
• Bilirubin < 1.8 mg/dl
• AST < 110 U/l
• ALT < 110 U/l
• Alkaline phosphatase < 300 U/l
• Subjects must weigh +/- 20% of ideal body weight by the Metropolitan Life tables
• Men or women who are strict vegetarians or who eat more than 3 medium servings (1/2 cup each) of cruciferous vegetables per week will be excluded; those who stop ingesting cruciferous vegetables >= 14 days and alcohol >= 7 days before starting DIM and agree to refrain from taking them for the duration of the study will not be excluded; cruciferous vegetables include broccoli, cabbage (including coleslaw), cauliflower, bok-choy, Brussels sprouts, collards, kale, kohlrabi, mustard greens, rutabaga, turnip, and watercress; participants will be asked to complete a brief diet questionnaire listing these vegetables to assess these criteria; caffeine- and grapefruit-containing foods and beverages are to be avoided for at least 48 hours before visit 2 (DIM dosing)

Exclusion Criteria:

• Subjects with serious drug allergies or other serious intolerance or allergies will be excluded; those with mild seasonal allergies will be accepted
• Subjects with chronic headaches, dysphoria, fatigue, dizziness, blurred vision, insomnia, rhinorrhea, nausea, vomiting, abdominal pain, diarrhea, constipation, or similar conditions
• Subjects with a serious acute or chronic illness (diabetes, arthritis, asthma, etc.) or requiring chronic drug therapy, who continuously take supplements or have taken an investigational drug within the past three months
• Subjects who have evidence of an active malignancy or have received chemotherapy, and/or antiestrogen therapy
• Subjects who have a life expectancy of < 12 months
• Subjects who have regularly taken over the past 21 days any concomitant medications, herbal products, dietary supplements or vitamins; women taking oral contraceptives will be accepted; women who are pregnant (positive urine human chorionic gonadotropin [hCG] at visit 2) or lactating will be excluded