Environmental Carcinogenesis
Conditions
Brief summary
This study will examine the extent to which lower doses of a broccoli-derived beverage enhance the detoxication of air pollutants excreted in urine as compared to an maximal dose shown to be effective previously.
Detailed description
This is a 10-day placebo control Phase II broccoli sprout intervention to be conducted in Qidong, P.R. China. Up to twelve hundred people from the farming townships will be screened and one hundred seventy eligible individuals will be enrolled in the study. Participants will be randomized into 4 treatment groups: one will receive a juice beverage containing a standard dose of glucoraphanin- and sulforaphane-rich broccoli sprout powder mixed in pineapple juice, lime juice and water, the second will receive one-half dose, the third one-fifth dose and the fourth group will receive placebo beverage containing pineapple juice, lime juice and water. Participants will drink their assigned beverage every evening and provide consecutive 12-hour urine collections throughout the duration of the study.
Interventions
DRUGBroccoli Sprout-derived Beverage
Maximum, half and one-fifth doses of broccoli sprout-derived beverage compared to placebos.
DRUGPlacebos
Placebo as comparison to broccoli sprout-derived beverages
Sponsors
Qidong Liver Cancer Institute
National Cancer Institute (NCI)
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
* in good general health with no history of chronic illness * normal liver function tests * normal renal function tests
Exclusion criteria
* personal history of cancer except for non-melanoma skin cancer * use of prescribed medicines * for women, a positive pregnancy test
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sulforaphane Bioavailability Measured in Sequential 12-Hour Urine Samples | 10 days | Urinary excretion of broccoli-derived sulforaphane metabolites: sulforaphane-mercapturic acid. The metabolites were measured all 20 of the sequential 12-hour urine collections from each participant over the 10-day intervention period. Data from each individual were summed to provide a single per 24-hours value for each participant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Modulation of Air Pollutant Excretion in Sequential Overnight 12-Hour Urine Samples | 10 days | Benzene-mercapturic acid (SPMA) excretion was measured in the sequential overnight 12-hour urine samples collected across the 10-day study period. Data from each individual were summed and averaged to provide a single per 12-hours value for each participant. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Beverage (100 mL) containing pineapple juice, lime juice and water. Nightly for 10 days.
Broccoli Sprout Powder: Maximum, half and one-fifth doses of broccoli sprout-derived beverage compared to placebo. | 55 |
| High Dose Broccoli Sprout Beverage (100 mL) containing glucoraphanin-rich (600 micromole) and sulforaphane-rich (40 micromole) broccoli sprout powder mixed in pineapple juice, lime juice and water. Nightly for 10 days.
Broccoli Sprout Powder: Maximum, half and one-fifth doses of broccoli sprout-derived beverage compared to placebo. | 25 |
| Medium Dose Broccoli Sprout Beverage (100 mL) containing glucoraphanin-rich (300 micromole) and sulforaphane-rich (20 micromole) broccoli sprout powder mixed in pineapple juice, lime juice and water. Nightly for 10 days.
Broccoli Sprout Powder: Maximum, half and one-fifth doses of broccoli sprout-derived beverage compared to placebo. | 35 |
| Low Dose Broccoli Sprout Beverage (100 mL) containing glucoraphanin-rich (120 micromole) and sulforaphane-rich (8 micromole) broccoli sprout powder mixed in pineapple juice, lime juice and water. Nightly for 10 days.
Broccoli Sprout Powder: Maximum, half and one-fifth doses of broccoli sprout-derived beverage compared to placebo. | 55 |
| Total | 170 |
Baseline characteristics
| Characteristic | High Dose Broccoli Sprout | Medium Dose Broccoli Sprout | Placebo | Low Dose Broccoli Sprout | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 35 Participants | 55 Participants | 55 Participants | 170 Participants |
| Age, Continuous | 59 years | 58 years | 56 years | 60 years | 58 years |
| Region of Enrollment China | 25 participants | 35 participants | 55 participants | 55 participants | 170 participants |
| Sex: Female, Male Female | 18 Participants | 28 Participants | 38 Participants | 43 Participants | 127 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 17 Participants | 12 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 55 | 0 / 25 | 0 / 35 | 0 / 55 |
| serious Total, serious adverse events | 0 / 55 | 0 / 25 | 0 / 35 | 0 / 55 |
Outcome results
Primary
Sulforaphane Bioavailability Measured in Sequential 12-Hour Urine Samples
Urinary excretion of broccoli-derived sulforaphane metabolites: sulforaphane-mercapturic acid. The metabolites were measured all 20 of the sequential 12-hour urine collections from each participant over the 10-day intervention period. Data from each individual were summed to provide a single per 24-hours value for each participant.
Time frame: 10 days
Population: Placebo arm samples were not analyzed f because no sulforaphane was administered to this group. Historically, background levels from dietary sources in this population are very low compared to active intervention levels. In addition, one participant in the High Dose Broccoli Sprout arm did not complete the full protocol and was not included.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| High Dose Broccoli Sprout | Sulforaphane Bioavailability Measured in Sequential 12-Hour Urine Samples | 24.8 micromoles/24 hours |
| Medium Dose Broccoli Sprout | Sulforaphane Bioavailability Measured in Sequential 12-Hour Urine Samples | 11.0 micromoles/24 hours |
| Low Dose Broccoli Sprout | Sulforaphane Bioavailability Measured in Sequential 12-Hour Urine Samples | 4.3 micromoles/24 hours |
Comparison: The null hypothesis is that the urinary sulforaphane levels are equal across treatment arms. Sulforaphane metabolite levels were measured daily for 10 days in each arm.p-value: <0.00195% CI: [-1.89, -1.57]Mixed Models Analysis
Secondary
Modulation of Air Pollutant Excretion in Sequential Overnight 12-Hour Urine Samples
Benzene-mercapturic acid (SPMA) excretion was measured in the sequential overnight 12-hour urine samples collected across the 10-day study period. Data from each individual were summed and averaged to provide a single per 12-hours value for each participant.
Time frame: 10 days
Population: Due to irreversible failure of the mass spectrometer used in this analysis, not all urine samples were evaluated for SPMA levels. Only individuals for whom all 10 samples were collected and analyzed are included in this summary (132/169).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Modulation of Air Pollutant Excretion in Sequential Overnight 12-Hour Urine Samples | 0.67 nmol SPMA excreted/ 12 hours |
| High Dose Broccoli Sprout | Modulation of Air Pollutant Excretion in Sequential Overnight 12-Hour Urine Samples | 0.62 nmol SPMA excreted/ 12 hours |
| Medium Dose Broccoli Sprout | Modulation of Air Pollutant Excretion in Sequential Overnight 12-Hour Urine Samples | 0.74 nmol SPMA excreted/ 12 hours |
| Low Dose Broccoli Sprout | Modulation of Air Pollutant Excretion in Sequential Overnight 12-Hour Urine Samples | 1.09 nmol SPMA excreted/ 12 hours |
Comparison: All broccoli sprout arms were compared with the placebo arm.p-value: <0.0595% CI: [10.6, 140.9]Regression, Linear