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Phase 1 Multiple-Dose Safety, Pharmacokinetic, and Drug Interaction Clinical Study of Nutritional-Grade, Absorption-Enhanced DIM (BR-DIM)


Phase 1
18 Years
70 Years
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

Thank you

Trial Information

Phase 1 Multiple-Dose Safety, Pharmacokinetic, and Drug Interaction Clinical Study of Nutritional-Grade, Absorption-Enhanced DIM (BR-DIM)


PRIMARY OBJECTIVES:

I. Determine the effect of multiple daily dosing with nutritional-grade, absorption-enhanced
diindolylmethane (BR-DIM) on the disposition of probe drugs metabolized by cytochrome
P4501A2 (CYP1A2) and CYP3A4 in healthy volunteers.

SECONDARY OBJECTIVES:

I. Determine the effect of multiple daily doses of BR-DIM on estrogen metabolites in urine
and on activities of CYP2C9, CYP2D6, and P-glycoprotein/OATP.

II. Determine the effect of a single dose of BR-DIM on the disposition of probe drugs that
are metabolized or transported by CYP1A2, CYP2C9, CYP2D6, CYP3A4, and P-glycoprotein (P-go).

III. Determine the safety and tolerability of single and multiple daily doses of BR-DIM.

IV. Determine the pharmacokinetics of a single dose of BR-DIM and of the same dose after
chronic daily dosing.

V. Determine the pharmacokinetics of a single dose of BR-DIM and of the same dose after
chronic daily dosing.

TERTIARY OBJECTIVES:

I. To determine effects of BR-DIM on activities of glutathione-S-transferase (GST), a phase
2 enzyme, in lymphocytes.

OUTLINE: This is a randomized, double-blind study. Participants are stratified according to
gender. Participants are randomized to 1 of 2 intervention arms.

Arm I: Participants receive low-dose oral diindolylmethane (BR-DIM) twice daily for 4 weeks.

Arm II: Participants receive high-dose oral BR-DIM twice daily for 4 weeks.

In both arms, participants receive an oral probe-drug cocktail comprising caffeine (CYP1A2),
dextromethorphan (CYP2D6), buspirone (CYP3A4), losartan (CYP2C9), and fexofenadine
(P-glycoprotein) before randomization and after the first and last dose of BR-DIM.

Blood and urine are collected periodically for pharmacokinetic profiles of BR-DIM and probe
drugs.

After completion of study intervention, participants are followed at 1 week.

Inclusion Criteria


Criteria:

- Healthy men and women

- Nonsmoker confirmed by urine cotinine test

- No active malignancy

- Life expectancy >= 12 months

- Hemoglobin > 10 g/dL

- Absolute granulocyte count > 1,500/mm^3

- 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

- Body mass index =< 30

- Not pregnant or nursing

- Negative pregnancy test

- Fertile participants must use effective nonhormonal contraception

- No acute, unstable, chronic, or recurring medical conditions

- No strict vegetarians or consumption of > 3 medium servings (1/2 cup each) of
cruciferous vegetables per week

- Participants who have stopped eating cruciferous vegetables within the past 2 weeks
and agree to refrain from eating them for the duration of the study are eligible

- Cruciferous vegetables include broccoli, cabbage (including coleslaw), cauliflower,
bok-choy, brussels sprouts, collards, kale, kohlrabi, mustard greens, rutabaga,
turnip, and watercress

- No serious drug allergies or other serious intolerance or allergies

- Mild seasonal allergies allowed

- No chronic conditions, including headaches, dysphoria, fatigue, dizziness, blurred
vision, insomnia, rhinorrhea, nausea, vomiting, abdominal pain, diarrhea,
constipation, menopausal hot flashes/night sweats, or clinically significant
premenstrual syndrome

- No serious acute or chronic illness

- No requirement for chronic drug therapy

- No alcohol ingestion within 48 hours of study treatment

- No investigational drugs within the past 3 months

- No prior chemotherapy

- No concurrent regular medications or hormones

- No recent change in medications or dosage of medications

- No concurrent regular supplements or vitamins

- No concurrent over-the-counter medications

- No concurrent grapefruit or its juice

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Outcome Measure:

Effect of diindolylmethane (BR-DIM) on activities of CYP3A4 and CYP1A2

Outcome Description:

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. Paired t-tests will be used to compare enzyme levels post-pre at each dose. Analysis of covariance will be used to determine if there is a dose effect on enzyme levels, using the baseline values as a covariate. If there is no dose effect, the seven subjects at each dose will be pooled which will provide an increase power to detect meaningful changes in enzyme levels.

Outcome Time Frame:

Up to 1 week

Safety Issue:

No

Principal Investigator

Reed Greg

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Kansas

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00867

NCT ID:

NCT00392652

Start Date:

November 2006

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific

Name

Location

University of Kansas Medical CenterKansas City, Kansas  66160-7353