Diindolylmethane in Preventing Cancer in Healthy Volunteers

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Healthy, no Evidence of Disease

Intervention / Treatment
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* Drug: diindolylmethane
* Other: placebo
* Other: pharmacological study
* Other: laboratory biomarker analysis
* Other: quality-of-life assessment


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (diindolylmethane)<br>Participants receive a single dose of diindolylmethane PO on day 1. | Drug: diindolylmethane<br>* Given PO<br>* Other names: DIM;Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Other: laboratory biomarker analysis<br>* Correlative studies<br>Other: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;|
| Placebo Comparator: Arm II (placebo)<br>Participants receive a single dose of placebo orally (PO) on day 1. | Other: placebo<br>* Given PO<br>* Other names: PLCB;Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Other: laboratory biomarker analysis<br>* Correlative studies<br>Other: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD), defined as the highest dose at which no grade 2 or higher toxicities are seen | Frequencies and percents will be used to summarize the toxicities seen at each dose level and overall. 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. | Up to day 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of diindolylmethane | Pharmacokinetic parameters such as half-life, maximum concentration (Cmax), time of Cmax (Tmax), and area under the concentration-time curve (AUC) will be calculated for all subjects who complete the study. It is anticipated that a one-compartment elimination model will fit the data. These parameters will be summarized at each dose and overall with median and ranges. | Baseline and at 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after administration |