Diindolylmethane in Healthy Volunteers
Açar sözlər
Mücərrəd
Təsvir
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.
Tarixlər
Son Doğrulandı: | 11/30/2016 |
İlk təqdim: | 10/24/2006 |
Təxmini qeydiyyat təqdim edildi: | 10/24/2006 |
İlk Göndərmə: | 10/25/2006 |
Son Yeniləmə Göndərildi: | 12/27/2016 |
Son Yeniləmə Göndərildi: | 12/28/2016 |
Həqiqi Təhsilin Başlama Tarixi: | 10/31/2006 |
Təxmini İlkin Tamamlanma Tarixi: | 09/30/2008 |
Təxmini İşin Tamamlanma Tarixi: | 09/30/2009 |
Vəziyyət və ya xəstəlik
Müdaxilə / müalicə
Drug: oral microencapsulated diindolylmethane
Faza
Qol Qrupları
Qol | Müdaxilə / müalicə |
---|---|
Experimental: Arm I (low-dose oral diindolylmethane) Participants receive low-dose oral diindolylmethane (BR-DIM) twice daily for 4 weeks. | |
Experimental: Arm II (high-dose oral diinolylmethane) Participants receive high-dose oral BR-DIM twice daily for 4 weeks. |
Uyğunluq Kriteriyaları
Təhsil üçün uyğun yaşlar | 18 Years Üçün 18 Years |
Təhsilə Uyğun Cinslər | All |
Sağlam Könüllüləri qəbul edir | Bəli |
Kriteriyalar | 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 |
Nəticə
İlkin nəticə tədbirləri
1. Effect of diindolylmethane (BR-DIM) on activities of CYP3A4 and CYP1A2 [Up to 1 week]
2. Grade 2 or higher toxicities, graded using NCI CTC version 2.0 [Up to 1 week]
3. Steady-state pharmacokinetic parameters such as half-life, Cmax, Tmax, and AUC [Up to 1 week]
İkincili Nəticə Tədbirləri
1. Drug metabolizing enzyme values (CYP2C9, CYP2D6, P-glycoprotein/OATP, and glutathione-S-transferase) [Up to 1 week]
2. 2/16 alpha OHE ratio in urine [Up to 1 month]