Clinical trial NCT00784394: Diindolylmethane in Preventing Cancer in Healthy Volunteers
Official title: Phase I Ascending Single Dose Pharmacokinetics (PK) and Safety Study of 3,3' Di-indolylmethane (DIM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy, no Evidence of Disease
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2008-11-04
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum tolerated dose (MTD), defined as the highest dose at which no grade 2 or higher toxicities are seen
timeFrame: Up to day 6
Secondary outcomes:
measure: Pharmacokinetics of diindolylmethane
timeFrame: Baseline and at 0.5, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after administration
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
Study officials:
affiliation: University of Kansas Medical Center
name: Aryeh Hurwitz
role: PRINCIPAL_INVESTIGATOR
References: