Broccoli Sprout/Broccoli Seed Extract Supplement in Decreasing Toxicity in Heavy Smokers
Primary Purpose
Cigarette Smoking-Related Carcinoma, Tobacco-Related Carcinoma
Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Broccoli Sprout/Broccoli Seed Extract Supplement
Laboratory Biomarker Analysis
Questionnaire Administration
Sponsored by

About this trial
This is an interventional prevention trial for Cigarette Smoking-Related Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Current tobacco smokers with >= 20 pack years of self-reported smoking exposure and a current average use of >= 10 cigarettes/day
- Karnofsky performance scale >= 70%
- Leukocytes >= 3,000/microliter
- Absolute neutrophil count >= 1,500/microliter
- Platelets >= 100,000/microliter
- Total bilirubin =< 2 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x ULN
- Creatinine =< ULN
- Fertile subjects must use adequate contraception (abstinence, barrier methods, or birth control pills) prior to study entry and for the duration of study participation; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- History of invasive cancer within the past 2 years, with the exception of excised and cured non-melanoma skin cancer or carcinoma in situ of the cervix
- Chronic, current or recent (within the past 2 weeks) use of systemic steroid doses equivalent to prednisone > 5 mg daily for continued use > 14 days; use of inhaled steroids, nasal sprays, and topical creams for small body areas is allowed
- Participants may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Avmacol
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant or lactating women
Sites / Locations
- Banner University Medical Center - Tucson
- University of Arizona Cancer Center - Prevention Research Clinic
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm I (Avmacol lower dose, Avmacol higher dose)
Arm II (Avmacol higher dose, Avmacol lower dose)
Arm Description
Participants receive lower dose broccoli sprout/broccoli seed extract supplement PO daily for 10-14 days. After 10-14 days, participants receive higher dose broccoli sprout/broccoli seed extract supplement PO daily for 10-14 days.
Participants receive higher dose broccoli sprout/broccoli seed extract supplement PO daily for 10-14 days. After 10-14 days, participants receive lower dose broccoli sprout/broccoli seed extract supplement PO daily for 10-14 days.
Outcomes
Primary Outcome Measures
Change in Urinary Excretion of the Mercapturic Acid of Benzene Following 4 Tablets Per Day of Avmacol
Change in the overnight urinary excretion the mercapturic acid of benzene following 4 tablets per day of Avmacol. Data presented as ratio of the geometric mean of overnight urinary excretion the mercapturic acid of benzene between post intervention and baseline.
Change in Urinary Excretion of the Mercapturic Acid of Benzene Following 8 Tablets Per Day of Avmacol
Change in the overnight urinary excretion the mercapturic acid of benzene following 8 tablets per day of Avmacol. Data presented as ratio of the geometric mean of overnight urinary excretion the mercapturic acid of benzene between post intervention and baseline.
Secondary Outcome Measures
Change in the Urinary Excretion of the Mercapturic Acids of Acrolein and Crotonaldehyde
Change following 4 tablets per day and 8 tablets per day of Avmacol wad determined separately. Data presented as ratio of the geometric mean of overnight urinary excretion of the mercapturic acid of acrolein/crotonaldehyde between post intervention and baseline.
Change in the NRF2 Target Gene Transcripts
Change in the expression of NQO1 in the buccal cells after 8 tablets per day of Avmacol. Data presented as ratio of the geometric mean of the gene expression of NQO1 between post intervention and baseline.
Dose-response Relationship Between Avmacol Dose and Detoxification of Tobacco Carcinogens
Dose-response relationship between the Avmacol dose and the detoxification of tobacco carcinogens. Data presented as ratio of percent change of the overnight urinary excretion of mercapturic acid of benzene/acrolein/crotonaldehyde between the 8 tables and 4 tables dose.
Systemic Study Agent Exposure
Change in the total urinary levels of sulforaphane and its glutathione-derived metabolites (i.e., the sum of the molar concentrations of sulforaphane and its glutathione-derived metabolites in urine). Data presented as ratio of the geometric mean of the total urinary levels of sulforaphane and its metabolites between post intervention and baseline.
Full Information
NCT ID
NCT03402230
First Posted
January 17, 2018
Last Updated
June 2, 2023
Sponsor
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT03402230
Brief Title
Broccoli Sprout/Broccoli Seed Extract Supplement in Decreasing Toxicity in Heavy Smokers
Official Title
Clinical Study of Avmacol® for Detoxification of Tobacco Carcinogens in Heavy Smokers
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
February 20, 2018 (Actual)
Primary Completion Date
January 10, 2020 (Actual)
Study Completion Date
July 24, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This randomized early phase I trial studies how well broccoli sprout/broccoli seed extract supplement works in decreasing toxicity in heavy smokers. Broccoli sprout/broccoli seed extract supplement is a dietary supplement made from broccoli sprout and seed extract powder, and may break down some of the cancer causing substances in tobacco smoke and produce substances that may protect cells from tobacco smoke-induced damage in current smokers.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine whether broccoli sprout/broccoli seed extract supplement (Avmacol) increases the urinary excretion of the mercapturic acid of the tobacco carcinogen, benzene, in healthy volunteers who are current heavy smokers.
SECONDARY OBJECTIVES:
I. To determine whether Avmacol increases the urinary excretion of the mercapturic acids of other tobacco carcinogens, including acrolein and crotonaldehyde.
II. To determine whether Avmacol increases the urinary excretion of the mercapturic acids of tobacco carcinogens, normalized by bio-measurement of tobacco exposure.
III. To determine whether Avmacol upregulates the NRF2 target gene transcripts in the buccal cells of current smokers.
IV. To evaluate for a dose-response relationship between Avmacol and the detoxification of tobacco carcinogens and the expression of NRF2 target gene transcripts.
V. To determine the relationship between systemic study agent exposure and biomarker modulation.
EXPLORATORY OBJECTIVES:
I. To determine whether the GSTM1 and GSTT1 genotypes are important genetic modulators of detoxification of tobacco carcinogens with Avmacol treatment.
II. To bank specimens for future research including evaluation of tobacco gene signatures in buccal and nasal epithelium and buccal cell nuclear morphometry.
OUTLINE: Participants are randomized into 1 of 2 arms.
ARM I: Participants receive lower dose broccoli sprout/broccoli seed extract supplement orally (PO) daily for 10-14 days. After 10-14 days, participants receive higher dose broccoli sprout/broccoli seed extract supplement PO daily for 10-14 days.
ARM II: Participants receive higher dose broccoli sprout/broccoli seed extract supplement PO daily for 10-14 days. After 10-14 days, participants receive lower dose broccoli sprout/broccoli seed extract supplement PO daily for 10-14 days.
After completion of study, participants are followed up at 10-14 days.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cigarette Smoking-Related Carcinoma, Tobacco-Related Carcinoma
7. Study Design
Primary Purpose
Prevention
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I (Avmacol lower dose, Avmacol higher dose)
Arm Type
Experimental
Arm Description
Participants receive lower dose broccoli sprout/broccoli seed extract supplement PO daily for 10-14 days. After 10-14 days, participants receive higher dose broccoli sprout/broccoli seed extract supplement PO daily for 10-14 days.
Arm Title
Arm II (Avmacol higher dose, Avmacol lower dose)
Arm Type
Experimental
Arm Description
Participants receive higher dose broccoli sprout/broccoli seed extract supplement PO daily for 10-14 days. After 10-14 days, participants receive lower dose broccoli sprout/broccoli seed extract supplement PO daily for 10-14 days.
Intervention Type
Drug
Intervention Name(s)
Broccoli Sprout/Broccoli Seed Extract Supplement
Other Intervention Name(s)
Avmacol
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Change in Urinary Excretion of the Mercapturic Acid of Benzene Following 4 Tablets Per Day of Avmacol
Description
Change in the overnight urinary excretion the mercapturic acid of benzene following 4 tablets per day of Avmacol. Data presented as ratio of the geometric mean of overnight urinary excretion the mercapturic acid of benzene between post intervention and baseline.
Time Frame
Baseline up to 14 days post intervention
Title
Change in Urinary Excretion of the Mercapturic Acid of Benzene Following 8 Tablets Per Day of Avmacol
Description
Change in the overnight urinary excretion the mercapturic acid of benzene following 8 tablets per day of Avmacol. Data presented as ratio of the geometric mean of overnight urinary excretion the mercapturic acid of benzene between post intervention and baseline.
Time Frame
Baseline up to 14 days post intervention
Secondary Outcome Measure Information:
Title
Change in the Urinary Excretion of the Mercapturic Acids of Acrolein and Crotonaldehyde
Description
Change following 4 tablets per day and 8 tablets per day of Avmacol wad determined separately. Data presented as ratio of the geometric mean of overnight urinary excretion of the mercapturic acid of acrolein/crotonaldehyde between post intervention and baseline.
Time Frame
Baseline up to 14 days post intervention
Title
Change in the NRF2 Target Gene Transcripts
Description
Change in the expression of NQO1 in the buccal cells after 8 tablets per day of Avmacol. Data presented as ratio of the geometric mean of the gene expression of NQO1 between post intervention and baseline.
Time Frame
Baseline up to 14 days post intervention
Title
Dose-response Relationship Between Avmacol Dose and Detoxification of Tobacco Carcinogens
Description
Dose-response relationship between the Avmacol dose and the detoxification of tobacco carcinogens. Data presented as ratio of percent change of the overnight urinary excretion of mercapturic acid of benzene/acrolein/crotonaldehyde between the 8 tables and 4 tables dose.
Time Frame
Up to 14 days post intervention
Title
Systemic Study Agent Exposure
Description
Change in the total urinary levels of sulforaphane and its glutathione-derived metabolites (i.e., the sum of the molar concentrations of sulforaphane and its glutathione-derived metabolites in urine). Data presented as ratio of the geometric mean of the total urinary levels of sulforaphane and its metabolites between post intervention and baseline.
Time Frame
Up to 14 days post intervention
Other Pre-specified Outcome Measures:
Title
GSTM1 and GSTT1 Genotypes
Description
Change in the urinary excretion of the mercapturic acids of tobacco carcinogens by GSTM1 and GSTT1 genotype. Data presented as ratio of the geometric mean of urinary excretion of mercapturic acid of benzene between post intervention and baseline for each genotype.
Time Frame
Up to 14 days post intervention
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Current tobacco smokers with >= 20 pack years of self-reported smoking exposure and a current average use of >= 10 cigarettes/day
Karnofsky performance scale >= 70%
Leukocytes >= 3,000/microliter
Absolute neutrophil count >= 1,500/microliter
Platelets >= 100,000/microliter
Total bilirubin =< 2 x institutional upper limit of normal (ULN)
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x ULN
Creatinine =< ULN
Fertile subjects must use adequate contraception (abstinence, barrier methods, or birth control pills) prior to study entry and for the duration of study participation; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
History of invasive cancer within the past 2 years, with the exception of excised and cured non-melanoma skin cancer or carcinoma in situ of the cervix
Chronic, current or recent (within the past 2 weeks) use of systemic steroid doses equivalent to prednisone > 5 mg daily for continued use > 14 days; use of inhaled steroids, nasal sprays, and topical creams for small body areas is allowed
Participants may not be receiving any other investigational agents
History of allergic reactions attributed to compounds of similar chemical or biologic composition to Avmacol
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant or lactating women
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julie E Bauman
Organizational Affiliation
The University of Arizona Medical Center-University Campus
Official's Role
Principal Investigator
Facility Information:
Facility Name
Banner University Medical Center - Tucson
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85719
Country
United States
Facility Name
University of Arizona Cancer Center - Prevention Research Clinic
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85719
Country
United States
12. IPD Sharing Statement
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Broccoli Sprout/Broccoli Seed Extract Supplement in Decreasing Toxicity in Heavy Smokers
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