Diindolylmethane in Healthy Volunteers - Full Text View

Sponsors and Collaborators:	University of Kansas National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00392652

Purpose

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 randomized phase I trial is studying the side effects and best dose of diindolylmethane in healthy volunteers.

Condition	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: oral microencapsulated diindolylmethane Other: pharmacological study	Phase I

MedlinePlus related topics: Cancer Urine and Urination

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double-Blind
Official Title:	Phase 1 Multiple-Dose Safety, Pharmacokinetic, and Drug Interaction Clinical Study of Nutritional-Grade, Absorption-Enhanced DIM (BR-DIM)

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Effect of diindolymethane (BR-DIM™) on activities of CYP3A4 and CYP1A2 [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Estrogen metabolites in urine and activities of CYP2C9, CYP2D6, P-glycoprotein/OATP, and glutathione-S-transferase [ Designated as safety issue: No ]
Safety and tolerability [ Designated as safety issue: Yes ]
Pharmacokinetics [ Designated as safety issue: No ]

Estimated Enrollment:	14
Study Start Date:	November 2006
Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

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

Determine the effect of BR-DIM™ on estrogen metabolites in urine and on activities of CYP2C9, CYP2D6, and P-glycoprotein/OATP.
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.
Determine the safety and tolerability of single and multiple daily doses of this drug in healthy volunteers.
Determine the pharmacokinetics of a single dose of BR-DIM™ and of the same dose after chronic daily dosing.
Determine the effects of BR-DIM™ on activities of glutathione-S-transferase, 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.

PROJECTED ACCRUAL: A total of 14 participants will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

DISEASE CHARACTERISTICS:

Healthy men and women
Nonsmoker confirmed by urine cotinine test
No active malignancy

PATIENT CHARACTERISTICS:

Life expectancy ≥ 12 months
Hemoglobin > 10 g/dL
Absolute granulocyte count > 1,500/mm³
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 (½ 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

PRIOR CONCURRENT THERAPY:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00392652

Locations

United States, Kansas
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-7357

Sponsors and Collaborators

University of Kansas

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Gregory Reed, PhD

University of Kansas

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000511393, KUMC-HSC-9139-3
Study First Received:	October 25, 2006
Last Updated:	February 7, 2009
ClinicalTrials.gov Identifier:	NCT00392652 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific

Study placed in the following topic categories:

Healthy

ClinicalTrials.gov processed this record on May 07, 2009