Clinical trial NCT03402230: 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
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Cigarette Smoking-Related Carcinoma
Tobacco-Related Carcinoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2018-01-18
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Change in Urinary Excretion of the Mercapturic Acid of Benzene Following 4 Tablets Per Day of Avmacol
timeFrame: Baseline up to 14 days post intervention
measure: Change in Urinary Excretion of the Mercapturic Acid of Benzene Following 8 Tablets Per Day of Avmacol
timeFrame: Baseline up to 14 days post intervention
Secondary outcomes:
measure: Change in the Urinary Excretion of the Mercapturic Acids of Acrolein and Crotonaldehyde
timeFrame: Baseline up to 14 days post intervention
measure: Change in the NRF2 Target Gene Transcripts
timeFrame: Baseline up to 14 days post intervention
measure: Dose-response Relationship Between Avmacol Dose and Detoxification of Tobacco Carcinogens
timeFrame: Up to 14 days post intervention
measure: Systemic Study Agent Exposure
timeFrame: Up to 14 days post intervention
Other outcomes:
measure: GSTM1 and GSTT1 Genotypes
timeFrame: Up to 14 days post intervention
Locations:
city: Tucson
country: United States
facility: Banner University Medical Center - Tucson
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Cancer Center - Prevention Research Clinic
state: Arizona
Study officials:
affiliation: The University of Arizona Medical Center-University Campus
name: Julie E Bauman
role: PRINCIPAL_INVESTIGATOR
References: