Back to results

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

About this trial

This is an interventional prevention trial for Cigarette Smoking-Related Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

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

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

Arm Title

Arm II (Avmacol higher dose, Avmacol lower dose)

Arm Type

Experimental

Arm Description

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

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

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

Time Frame

Baseline up to 14 days post intervention

Title

Change in the NRF2 Target Gene Transcripts

Description

Time Frame

Baseline up to 14 days post intervention

Title

Dose-response Relationship Between Avmacol Dose and Detoxification of Tobacco Carcinogens

Description

Time Frame

Up to 14 days post intervention

Title

Systemic Study Agent Exposure

Description

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

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

Learn more about this trial

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

We'll reach out to this number within 24 hrs