Phase I Ascending Single Dose Pharmacokinetics (PK) and Safety Study of 3,3' Di-indolylmethane (DIM)
- 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
- 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
- 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
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.
Masking: Double-Blind, Primary Purpose: Prevention
Safety and toxicity of oral microencapsulated diindolylmethane (DIM) as assessed by NCI CTC v2.0
Aryeh Hurwitz, MD
University of Kansas
United States: Federal Government