Environmental Carcinogenesis
Conditions
Keywords
glucoraphanin, sulforaphane, pharmacokinetics, pharmacodynamics, broccoli sprout, carcinogens, environment
Brief summary
This study is a 12 week placebo-controlled Phase II broccoli sprout intervention to be conducted in Qidong, P.R. China. One thousand two hundred people from the farming townships will be screened and three hundred eligible individuals will be enrolled in the study. Participants will be randomized into two treatment groups: one will receive a juice beverage containing glucoraphanin- and sulforaphane-rich broccoli sprout extract, pineapple juice, lime juice, and water and the other will receive a placebo beverage containing pineapple juice, lime juice and water. Participants will drink their assigned beverage every evening and provide biweekly urine samples and monthly blood samples. The principal endpoints of this study are pharmacokinetic evaluation of elimination of glucoraphanin/sulforaphane and their metabolites in urine and pharmacodynamic evaluation through measures of urinary levels of exposure biomarkers for dietary and air-borne toxins, which are known to be high in this population.
Interventions
DRUGBroccoli Sprout Extract Beverage
Broccoli Sprout Extract Beverage: 600 micromole glucoraphanin and 40 micromole sulforaphane dissolved in 100 mL dilute pineapple and lime juice daily for 84 days.
DRUGplacebo beverage
100 mL of dilute pineapple and lime juice daily for 84 days.
Sponsors
Johns Hopkins University
National Institute of Environmental Health Sciences (NIEHS)
Qidong Liver Cancer Institute
University of Pittsburgh
University of Minnesota
Johns Hopkins Bloomberg School of Public Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* age 21-65 years * in good general health with no history of chronic illness * normal liver function tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin) * normal renal function tests (creatinine, blood urea nitrogen, urinalysis) * serum alpha-fetoprotein negative
Exclusion criteria
* personal history of cancer except for non-melanoma skin cancer * use of prescribed medications * hepatomegaly by clinical exam * for women, a positive pregnancy test
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Treatment on Levels of Air Toxics Mercapturic Acids Over Intervention Period | Endpoints were assessed on urine samples collected at the end of the intervention on week 12. | Urinary excretion of benzene mercapturic acid (S-PMA) in 12 hour overnight void at 12 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Levels of Sulforaphane and Its Metabolites at the End of Intervention Period (After 84 Daily Doses) | Endpoints assessed on urine samples collected at the end of the intervention (day 84 [week 12]) | Micromoles of urinary sulforaphane metabolites excreted over 24 hours after consuming the 84th dose. |
Countries
China
Participant flow
Recruitment details
1205 Individuals were recruited from HeHe Township in Qidong, PRC for eligibility screening at 3 medical clinics within the township in September 2011.
Participants by arm
| Arm | Count |
|---|---|
| Broccoli Sprout Extract Beverage Broccoli Sprout Extract Beverage : Broccoli Sprout Extract Beverage: 600 micromole glucoraphanin and 40 micromole sulforaphane dissolved in 100 mL dilute pineapple and lime juice daily for 84 days. | 148 |
| Placebo Beverage placebo beverage : 100 mL of dilute pineapple and lime juice daily for 84 days. | 143 |
| Total | 291 |
Baseline characteristics
| Characteristic | Placebo Beverage | Broccoli Sprout Extract Beverage | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 143 Participants | 148 Participants | 291 Participants |
| Age, Continuous | 52.6 years STANDARD_DEVIATION 7.7 | 51.1 years STANDARD_DEVIATION 9.4 | 51.8 years STANDARD_DEVIATION 8.7 |
| Region of Enrollment China | 143 participants | 148 participants | 291 participants |
| Sex: Female, Male Female | 111 Participants | 118 Participants | 229 Participants |
| Sex: Female, Male Male | 32 Participants | 30 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 148 | 4 / 143 |
| serious Total, serious adverse events | 0 / 148 | 0 / 143 |
Outcome results
Primary
Effect of Treatment on Levels of Air Toxics Mercapturic Acids Over Intervention Period
Urinary excretion of benzene mercapturic acid (S-PMA) in 12 hour overnight void at 12 weeks
Time frame: Endpoints were assessed on urine samples collected at the end of the intervention on week 12.
Population: Analyses were conducted on all urine samples provided by study participants at week 12.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Broccoli Sprout Extract Beverage | Effect of Treatment on Levels of Air Toxics Mercapturic Acids Over Intervention Period | 1.700 pmol/mg creatinine |
| Placebo Beverage | Effect of Treatment on Levels of Air Toxics Mercapturic Acids Over Intervention Period | 1.065 pmol/mg creatinine |
Secondary
Levels of Sulforaphane and Its Metabolites at the End of Intervention Period (After 84 Daily Doses)
Micromoles of urinary sulforaphane metabolites excreted over 24 hours after consuming the 84th dose.
Time frame: Endpoints assessed on urine samples collected at the end of the intervention (day 84 [week 12])
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Broccoli Sprout Extract Beverage | Levels of Sulforaphane and Its Metabolites at the End of Intervention Period (After 84 Daily Doses) | 1 micromoles |
| Placebo Beverage | Levels of Sulforaphane and Its Metabolites at the End of Intervention Period (After 84 Daily Doses) | 62 micromoles |