CompletedNCT03402230Updated Jun 28, 2023Results posted

Broccoli Sprout/Broccoli Seed Extract Supplement in Decreasing Toxicity in Heavy Smokers

An Early Phase 1 interventional study of Broccoli Sprout/Broccoli Seed Extract Supplement and Laboratory Biomarker Analysis in Cigarette Smoking-Related Carcinoma and Tobacco-Related Carcinoma, sponsored by National Cancer Institute (NCI). Completed at 2 sites in United States. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-06-28.

Sponsored by National Cancer Institute (NCI) · Early Phase 1, Interventional, and Prevention

Phase: Early Phase 1
Study type: Interventional
Enrollment: 49
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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.

Read the 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.

Conditions studied

Cigarette Smoking-Related Carcinoma
Tobacco-Related Carcinoma

Browse trials for

Carcinoma 6,766

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: Yes

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

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

Study design

Phase: Early Phase 1
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 49 participants (actual)

Study arms

Experimental
Arm I (Avmacol lower dose, Avmacol higher dose)
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.
Drug: Broccoli Sprout/Broccoli Seed Extract Supplement · Other: Laboratory Biomarker Analysis · Other: Questionnaire Administration
Experimental
Arm II (Avmacol higher dose, Avmacol lower dose)
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.
Drug: Broccoli Sprout/Broccoli Seed Extract Supplement · Other: Laboratory Biomarker Analysis · Other: Questionnaire Administration

Interventions

DrugBroccoli Sprout/Broccoli Seed Extract Supplement
Given PO
Also known as: Avmacol
OtherLaboratory Biomarker Analysis
Correlative studies
OtherQuestionnaire Administration
Ancillary studies

What researchers measure

Primary outcomes

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.
Time frame: Baseline up to 14 days post intervention
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.
Time frame: Baseline up to 14 days post intervention

Secondary outcomes

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.
Time frame: Baseline up to 14 days post intervention
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.
Time frame: Baseline up to 14 days post intervention
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.
Time frame: Up to 14 days post intervention
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.
Time frame: Up to 14 days post intervention

Other outcomes

GSTM1 and GSTT1 Genotypes
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

Results

Posted Apr 30, 2021

Participant flow

Participant flow — Overall Study
Milestone	Avmacol Low Dose First, Then High Dose	Avmacol High Dose First, Then Low Dose
Started	25	24
Completed	25	23
Not completed	0	1

Outcome measures

PrimaryChange 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.

Time frame:: Baseline up to 14 days post intervention
Reported as:: Number · data presented as ratio; no unit

Change in Urinary Excretion of the Mercapturic Acid of Benzene Following 4 Tablets Per Day of Avmacol
data presented as ratio; no unit	Avmacol
Change in Urinary Excretion of the Mercapturic Acid of Benzene Following 4 Tablets Per Day of Avmacol	1.16 (0.998 to 1.344)

PrimaryChange 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.

Time frame:: Baseline up to 14 days post intervention
Reported as:: Number · data presented as ratio; no unit

Change in Urinary Excretion of the Mercapturic Acid of Benzene Following 8 Tablets Per Day of Avmacol
data presented as ratio; no unit	Avmacol
Change in Urinary Excretion of the Mercapturic Acid of Benzene Following 8 Tablets Per Day of Avmacol	1.19 (1.005 to 1.409)

SecondaryChange 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.

Time frame:: Baseline up to 14 days post intervention
Reported as:: Number · data presented as ratio; no unit

Change in the Urinary Excretion of the Mercapturic Acids of Acrolein and Crotonaldehyde
data presented as ratio; no unit	Avmacol 4 Tablets	Avmacol 8 Tablets
Urindary excretion of mercapturic acid of acrolein	1.11 (0.98 to 1.26)	1.28 (1.06 to 1.53)
Urinary excretion of mercapturic acid of crotonaldehyde	1.05 (0.90 to 1.22)	1.18 (1.02 to 1.37)

SecondaryChange 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.

Time frame:: Baseline up to 14 days post intervention
Reported as:: Number · data presented as ratio; no unit

Change in the NRF2 Target Gene Transcripts
data presented as ratio; no unit	Avmacol 8 Tablets
Change in the NRF2 Target Gene Transcripts	1.00 (0.98 to 1.02)

SecondaryDose-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.

Time frame:: Up to 14 days post intervention
Reported as:: Number · data presented as ratio; no unit

Dose-response Relationship Between Avmacol Dose and Detoxification of Tobacco Carcinogens
data presented as ratio; no unit	Avmacol
Mercapturic acid of benzene	1.01 (0.89 to 1.15)
Mercapturic acid of acrolein	1.14 (0.95 to 1.36)
Mercapturic acid of crotonaldehyde	1.12 (0.95 to 1.32)

SecondarySystemic 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.

Time frame:: Up to 14 days post intervention
Reported as:: Number · data presented as ratio; no unit

Systemic Study Agent Exposure
data presented as ratio; no unit	Avmacol 4 Tablets	Avmacol 8 Tablets
Systemic Study Agent Exposure	467.9 (264.7 to 826.9)	990.0 (592.2 to 1655.1)

Other pre-specifiedGSTM1 and GSTT1 Genotypes

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
Reported as:: Number · data presented as ratio; no unit

GSTM1 and GSTT1 Genotypes
data presented as ratio; no unit	Avmacol 4 Tablets	Avmacol 8 Tablets
Mercapturic acid of benzene in GSTM1-null participants	1.23 (0.99 to 1.52)	1.34 (0.98 to 1.84)
Mercapturic acid of benzene in GSTM1-positive participants	1.10 (0.90 to 1.35)	1.06 (0.93 to 1.21)
Mercapturic acid of benzene in GSTT1-null participants	0.75 (0.54 to 1.04)	1.16 (0.89 to 1.51)
Mercapturic acid of benzene in GSTT1-positive participants	1.26 (1.08 to 1.47)	1.20 (0.98 to 1.45)

Adverse events

Collected over Two weeks of agent intervention. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
High Dose	0/49 (0%)	1/49 (2%)	26/49 (53.1%)
Low Dose	0/48 (0%)	0/48 (0%)	14/48 (29.2%)

Most frequent serious events

Most frequent serious events
Event	High Dose	Low Dose
Myocardial infarctionCardiac disorders	1/49	0/48

Most frequent other events

Most frequent other events
Event	High Dose	Low Dose
DiarrheaGastrointestinal disorders	10/49	3/48
Abdominal painGastrointestinal disorders	10/49	1/48
Gastrointestinal disorders, otherGastrointestinal disorders	9/49	7/48
FlatulenceGastrointestinal disorders	7/49	3/48
DyspepsiaGastrointestinal disorders	3/49	1/48

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Avmacol
Mean	56 ± 9

Sex: Female, Male
Sex: Female, Male(Participants)	Avmacol
Female	26
Male	23

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Avmacol
Hispanic or Latino	4
Not Hispanic or Latino	44
Unknown or Not Reported	1

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Avmacol
American Indian or Alaska Native	0
Asian	0
Native Hawaiian or Other Pacific Islander	0
Black or African American	1
White	44
More than one race	3
Unknown or Not Reported	1

Study locations

2 sites

Banner University Medical Center - Tucson
Tucson, Arizona 85719, United States
University of Arizona Cancer Center - Prevention Research Clinic
Tucson, Arizona 85719, United States

References and documents

Study documents

Protocol and statistical analysis plan · Oct 17, 2018

Documents are hosted by the registry — open the source record to download them.

Registry details

Key details

Study ID: NCT03402230
Lead sponsor: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Jan 18, 2018
Start date: Feb 20, 2018
Primary completion: Jan 10, 2020
Completion: Jul 24, 2022
Results posted: Apr 30, 2021
Last update: Jun 28, 2023

Study contacts

Julie E Bauman

principal investigator · The University of Arizona Medical Center-University Campus

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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