Phase I Ascending Single Dose Pharmacokinetics (PK) and Safety Study of 3,3' Di-indolylmethane (DIM)
18 Years
70 Years
Both
Healthy, no Evidence of Disease
Trial Information
Phase I Ascending Single Dose Pharmacokinetics (PK) and Safety Study of 3,3' Di-indolylmethane (DIM)
OBJECTIVES:
Primary
- To determine single oral doses of microencapsulated diindolylmethane (DIM) that are
safe and well-tolerated in healthy volunteers.
- To determine the pharmacokinetics of DIM in these participants.
- 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
- 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.
- 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.
- To determine the safety and tolerability of single and multiple daily doses of DIM.
- To determine the pharmacokinetics of a single dose of DIM and of the same dose after
chronic daily dosing.
Tertiary
- To determine effects of DIM on activities of glutathione-S-transferase (GST) and
quinone reductase (NQO1), and phase 2 enzymes in lymphocytes.
- 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).
- 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.
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.
Inclusion 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)
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
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
Type of Study:
Interventional
Study Design:
Masking: Double-Blind, Primary Purpose: Prevention
Outcome Measure:
Safety and toxicity of oral microencapsulated diindolylmethane (DIM) as assessed by NCI CTC v2.0
Safety Issue:
Yes
Principal Investigator
Aryeh Hurwitz, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Kansas
Authority:
United States: Federal Government
Study ID:
CDR0000617334
NCT ID:
NCT00784394
Start Date:
April 2004
Completion Date:
Related Keywords:
- Healthy, no Evidence of Disease
- healthy, no evidence of disease
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