Healthy, no Evidence of DiseasePhase 1NCT00392652
Diindolylmethane in Healthy Volunteers
A Phase 1 study testing oral microencapsulated diindolylmethane in people with Healthy, no Evidence of Disease, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This randomized phase I trial is studying the side effects and best dose of diindolylmethane in healthy volunteers. 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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy, no Evidence of Disease
- What is being tested?
- oral microencapsulated diindolylmethane
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2006to Oct 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kansas Medical Center
Kansas City, Kansas, 66160
About this study
Official title: Phase 1 Multiple-Dose Safety, Pharmacokinetic, and Drug Interaction Clinical Study of Nutritional-Grade, Absorption-Enhanced DIM (BR-DIM)
This randomized phase I trial is studying the side effects and best dose of diindolylmethane in healthy volunteers. 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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Determine the pharmacokinetics of a single dose of BR-DIM and of the same dose after chronic daily dosing.
TERTIARY OBJECTIVES:
- 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.
- Conditions
- Healthy, no Evidence of Disease
- Being tested
- oral microencapsulated diindolylmethane
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oral microencapsulated diindolylmethaneDrug
Also called BioResponse DIM, BR-DIM
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm I (low-dose oral diindolylmethane) | Experimental | Participants receive low-dose oral diindolylmethane (BR-DIM) twice daily for 4 weeks. Receives: Drug: oral microencapsulated diindolylmethane |
| Arm II (high-dose oral diinolylmethane) | Experimental | Participants receive high-dose oral BR-DIM twice daily for 4 weeks. Receives: Drug: oral microencapsulated diindolylmethane |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of diindolylmethane (BR-DIM) on activities of CYP3A4 and CYP1A2
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.
Measured: Up to 1 week
Grade 2 or higher toxicities, graded using NCI CTC version 2.0
A one-sided binomial test will be used. 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.
Measured: Up to 1 week
Steady-state pharmacokinetic parameters such as half-life, Cmax, Tmax, and AUC
Pharmacokinetic parameters between pre- and post-menopausal women will be compared using the Wilcoxon rank-sum test.
Measured: Up to 1 week
Secondary outcomes (2)
Drug metabolizing enzyme values (CYP2C9, CYP2D6, P-glycoprotein/OATP, and glutathione-S-transferase)
The probe drug values for the first three enzymes for the baseline (placebo) values and the first-dose BR-DIM values compared to assess inhibitory possible interactions, and between baseline and last-dose BR-DIM values to assess the possibility of either inhibitory or inductive events. Measurements of lymphocyte cytosolic GST activities will compare baseline to last-dose BR-DIM values, and thus assess the possibility of either inhibitory or inductive events. Since we anticipate skewed data, we will compare the values listed above using nonparametric Wilcoxon sign rank tests.
Measured: Up to 1 week
2/16 alpha OHE ratio in urine
A one-way repeated measures analysis of variance will be used to compare this ratio across treatment periods (baseline, one month on BR-DIM, one month after stopping BR-DIM). We will summarize 2/16 alpha OHE ratio at each dose by means and standard deviations. If there is a large degree of skewness the median and range will be utilized as summary measures and Friedman's test utilized to assess the effect of BR-DIM on metabolites of estrogen in urine.
Measured: Up to 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2006 (estimated)
- Study startNov 2006
- Primary completionOct 2008
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy, no Evidence of DiseaseStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Reed Greg, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00392652
- Sponsor's protocol ID
- NCI-2009-00867
- Other IDs
- NCI-2009-00867, CDR0000511393, HSC # 9139, HSC # 9139, N01-CN-35008-3, N01CN35008
- Status last verified
- Dec 2016
- First submitted
- 25 Oct 2006
- Last updated
- 29 Dec 2016
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Multiple-Dose Safety, Pharmacokinetic, and Drug Interaction Clinical Study of Nutritional-Grade, Absorption-Enhanced DIM (BR-DIM)
- ClinicalTrials.gov ID
- NCT00392652
- Acronym / sponsor ID
- NCI-2009-00867
- Conditions
- Healthy, no Evidence of Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Nov 2006
- Primary completion
- Oct 2008 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 26 Oct 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized phase I trial is studying the side effects and best dose of diindolylmethane in healthy volunteers. 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.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Determine the pharmacokinetics of a single dose of BR-DIM and of the same dose after chronic daily dosing.
TERTIARY OBJECTIVES:
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (low-dose oral diindolylmethane) | Experimental | Drug: oral microencapsulated diindolylmethaneParticipants receive low-dose oral diindolylmethane (BR-DIM) twice daily for 4 weeks. |
| Arm II (high-dose oral diinolylmethane) | Experimental | Drug: oral microencapsulated diindolylmethaneParticipants receive high-dose oral BR-DIM twice daily for 4 weeks. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| oral microencapsulated diindolylmethaneAlso: BioResponse DIM, BR-DIMGiven PO | Drug | Arm I (low-dose oral diindolylmethane), Arm II (high-dose oral diinolylmethane) |
Primary outcome
Effect of diindolylmethane (BR-DIM) on activities of CYP3A4 and CYP1A2
Time frame: Up to 1 week
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.
Grade 2 or higher toxicities, graded using NCI CTC version 2.0
Time frame: Up to 1 week
A one-sided binomial test will be used. 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.
Steady-state pharmacokinetic parameters such as half-life, Cmax, Tmax, and AUC
Time frame: Up to 1 week
Pharmacokinetic parameters between pre- and post-menopausal women will be compared using the Wilcoxon rank-sum test.
2 secondary outcomes
Drug metabolizing enzyme values (CYP2C9, CYP2D6, P-glycoprotein/OATP, and glutathione-S-transferase)
Time frame: Up to 1 week
2/16 alpha OHE ratio in urine
Time frame: Up to 1 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Reed Greg principal investigator
University of Kansas Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing oral microencapsulated diindolylmethane in people with Healthy, no Evidence of Disease, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of diindolylmethane (BR-DIM) on activities of CYP3A4 and CYP1A2 (time frame: Up to 1 week). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2016.