Diindolylmethane in Healthy Nonsmokers
Recruitment status was Active, not recruiting
RATIONALE: Chemoprevention is the use of certain drugs or substances to keep cancer from forming, growing, or coming back. The use of diindolylmethane may keep cancer from forming. Collecting and storing samples of blood and urine from healthy volunteers to study in the laboratory may help doctors learn more about the way a person's body handles the drug.
PURPOSE: This phase I trial is studying the side effects and best dose of diindolylmethane in healthy volunteers.
Healthy, no Evidence of Disease
Drug: oral microencapsulated diindolylmethane
Other: gas chromatography
Other: laboratory biomarker analysis
Other: liquid chromatography
Other: mass spectrometry
Other: pharmacological study
|Study Design:||Masking: Double-Blind
Primary Purpose: Prevention
|Official Title:||Phase I Ascending Single Dose Pharmacokinetics (PK) and Safety Study of 3,3' Di-indolylmethane (DIM)|
- Safety and toxicity of oral microencapsulated diindolylmethane (DIM) as assessed by NCI CTC v2.0 [ Designated as safety issue: Yes ]
- Maximum-tolerated dose of DIM [ Designated as safety issue: Yes ]
- Pharmacokinetics of DIM [ Designated as safety issue: No ]
|Study Start Date:||April 2004|
- 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.
- 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.
- 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.
|Principal Investigator:||Aryeh Hurwitz, MD||University of Kansas|